RESUMEN
RD is a serious and well-known complication after cataract surgery, developing in 1% to 3% of all patients undergoing cataract extraction. High myopia, disruption of the posterior capsule intraoperatively or postoperatively by Nd: YAG laser, and vitreous loss increases the risk for RD. Retinal evaluation with detailed indirect ophthalmoscopy with scleral indentation and prophylactic treatment to all lesions that contribute to retinal tear and RD is strongly advocated before cataract surgery and Nd: YAG laser capsulotomy. Intraoperative vitreous loss should be managed meticulously, and these patients should be examined more frequently in the postoperative period. During phacoemulsification, no attempts should be made to retrieve the dislocated nuclear fragments without proper vitrectomy. It is best advised that a vitreoretinal surgeon handles the complication. Early recognition and prompt treatment following the detachment can result in good visual recovery.
Asunto(s)
Desprendimiento de Retina , Extracción de Catarata/efectos adversos , Humanos , Miopía/complicaciones , Desprendimiento de Retina/etiología , Desprendimiento de Retina/cirugía , Factores de RiesgoRESUMEN
PURPOSE: To report a case series of penetrating injury complicated by occurrence of intraocular cilia. METHODS: Retrospective analysis of charts of 11 eyes of 11 patients with penetrating injury and intraocular cilia, presenting between September 1978 and November 1998. Ten eyes underwent surgery for trauma-related problems such as cataract, vitritis, retinal detachment etc., at which time intraocular cilia were removed. One eye did not have surgery and continues to harbour cilia at the posterior perforation site. RESULTS: Metallic wire was responsible for injury in 6 of 11 eyes with intraocular cilia. Five eyes had significant intraocular inflammation. The cilia were located in the anterior segment in 4 eyes; in the posterior segment in 6 eyes and in both in one eye. At the last follow up, 72.7% had 6/18 or better vision. Poor vision in the rest was due to recurrent retinal detachment (2 eyes) and macular scarring (1 eye). CONCLUSION: Intraocular cilia are more commonly associated with injury by a metallic wire. The presentation and management of an injured eye does not seem to be influenced by the presence of cilia in the eye.
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Segmento Anterior del Ojo/lesiones , Cuerpos Extraños en el Ojo/etiología , Lesiones Oculares Penetrantes/complicaciones , Pestañas , Cuerpo Vítreo/lesiones , Adolescente , Adulto , Niño , Cuerpos Extraños en el Ojo/patología , Cuerpos Extraños en el Ojo/cirugía , Lesiones Oculares Penetrantes/patología , Lesiones Oculares Penetrantes/cirugía , Femenino , Humanos , Cristalino/lesiones , Masculino , Metales , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate and compare the risks and benefits of autologous serum as an adjuvant therapy in macular hole surgery for stage 3 or 4 macular holes. METHODS: Comparison of 2 consecutive (nonrandomized) cohorts using standardized methods for the determination of hole size and for surgical procedures, and using the same study surgeons. The serum cohort consisted of 106 eyes using autologous serum as an adjuvant, and the no serum cohort consisted of 58 eyes without adjuvants. The primary end point was the closure of the macular hole as determined by the 6-month fundus photographs. Secondary end points included the number and types of postoperative complications. Comparison in outcomes between the 2 cohorts used chi2 and logistic regression procedures, adjusting for preoperative differences between the study cohorts. RESULTS: At 6 months, the (unadjusted) rate of hole closure was significantly greater for the eyes treated with serum than for the eyes not treated with serum (90 [85%] of 106 vs. 40 [69%] of 58, P = .04). However, after adjusting for preoperative differences in hole diameter and the prevalence of epiretinal membranes, no overall difference in hole closure rates due to serum was found (P = .44). In contrast, benefit due to serum for large holes (diameter >573 microm) was seen (12 [75%] of 16 vs 13 [57%] of 23, P = .04). No differences in complication rates were found between the cohorts. CONCLUSIONS: Any beneficial effect of serum used as an adjuvant to macular hole surgery is small, and, if present, the beneficial effect may be limited to larger holes. A randomized, prospective, controlled study in larger macular holes is needed.
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Sangre , Perforaciones de la Retina/terapia , Vitrectomía , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Angiografía con Fluoresceína , Fluorocarburos/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Perforaciones de la Retina/clasificaciónAsunto(s)
Ensayos Clínicos como Asunto/normas , Difusión de Innovaciones , Anafilaxia/inducido químicamente , Ensayos Clínicos como Asunto/economía , Hipersensibilidad a las Drogas/etiología , Fluoresceína/efectos adversos , Angiografía con Fluoresceína/normas , Humanos , Verde de Indocianina/efectos adversosRESUMEN
OBJECTIVE: To study the aqueous humor dynamics in subjects with human immunodeficiency virus (HIV) with and without cytomegalovirus (CMV) retinitis. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Fourteen HIV-positive subjects (27 eyes, 19 with CMV retinitis and 8 without CMV retinitis), and a control group of 9 HIV-negative subjects (17 eyes). TESTING: Fluorophotometry. MAIN OUTCOME MEASURES: Aqueous flow rates as measured by fluorophotometry and intraocular pressure (IOP). RESULTS: Analysis of variance of the mean corrected aqueous flow rate revealed that both HIV-positive groups had significantly lower aqueous flow rates than did the control group (P < 0.03). No difference in mean aqueous flow rates was found between the HIV-positive eyes with or without CMV retinitis. Comparison of mean IOP revealed that HIV-positive eyes with CMV retinitis had significantly lower IOP than did the HIV-positive eyes without CMV retinitis (P = 0.03) and HIV-negative subjects (P = 0.002). There was no correlation between aqueous flow rate and IOP in HIV-positive subjects (P > 0.5). CONCLUSION: The lack of correlation between the aqueous flow rate and IOP suggests that there may be some disassociation between these parameters in HIV-positive patients. Further studies are needed to better understand the mechanism of aqueous formation and in the management of disorders affecting IOP in this population.
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Infecciones Oportunistas Relacionadas con el SIDA/metabolismo , Humor Acuoso/metabolismo , Retinitis por Citomegalovirus/metabolismo , Fluorofotometría , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Cámara Anterior/metabolismo , Estudios Transversales , Retinitis por Citomegalovirus/complicaciones , Retinitis por Citomegalovirus/tratamiento farmacológico , Femenino , Humanos , Presión Intraocular , Masculino , Estudios ProspectivosRESUMEN
PURPOSE: To characterize the anterior segment effects of cidofovir, using an animal model. METHODS: Cidofovir drops, at concentrations of 0.04%, 0.4% and 4%, were instilled in eyes of guinea pigs once daily for 10 days. Fellow eyes (controls) received normal saline. The corneal epithelium was debrided at day one and then at every other day for 10 days. Subconjunctival injections of 20 microl of 4% cidofovir were given in another group of animals. A micromanometer was used to determine the intraocular pressure (IOP). Eyes were studied histopathologically at the conclusion of the study. RESULTS: There was no significant drop in IOP after 10 days, using the 0.04% concentration of cidofovir drops. Histology revealed mild corneal edema and inflammatory infiltrate; iris, ciliary body and retina were normal. There was a statistically significant drop in IOP in the eyes treated with 0.4% and 4.0% cidofovir eye drops at 10 days (p = 0.005 and p < 0.0001, respectively) compared to baseline. Morphological changes included moderate to severe corneal edema, vascularization and inflammatory infiltration. The iris and ciliary body revealed mild inflammatory changes only at the 4% cidofovir dose. No changes were seen in the retina with any doses. No change in IOP was observed following subconjunctival injections of 4% cidofovir, and histologically, only localized inflammatory changes in the conjunctiva were observed. CONCLUSIONS: The IOP-decreasing effect of cidofovir occurs at doses below those causing intraocular inflammation and is likely due to an effect on the anterior segment. The anterior segment effects of cidofovir in guinea pigs were similar to those in humans. Thus, the guinea pig appears to be a good animal model for studying the effects of cidofovir on the anterior segment structures.
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Antivirales/farmacología , Córnea/efectos de los fármacos , Edema Corneal/inducido químicamente , Citosina/análogos & derivados , Presión Intraocular/efectos de los fármacos , Organofosfonatos , Compuestos Organofosforados/farmacología , Administración Tópica , Animales , Antivirales/administración & dosificación , Cidofovir , Cuerpo Ciliar/efectos de los fármacos , Conjuntiva/efectos de los fármacos , Córnea/patología , Edema Corneal/patología , Citosina/administración & dosificación , Citosina/farmacología , Cobayas , Inyecciones , Iris/efectos de los fármacos , Queratitis/inducido químicamente , Queratitis/patología , Modelos Biológicos , Soluciones Oftálmicas , Compuestos Organofosforados/administración & dosificación , Retina/efectos de los fármacosRESUMEN
PURPOSE: To describe the results of management of glass intraocular foreign bodies (IOFBs). METHODS: A total of 51 eyes of 43 patients that sustained penetrating injury with glass IOFB were studied retrospectively. A total of 23.5% had IOFB only in the anterior segment; the rest had IOFB in the posterior segment alone or in both the anterior and posterior segments. Six eyes were followed conservatively despite IOFB in a functional eye. Removal of IOFB was combined with repair of retinal detachment (where present) using internal tamponade with gas or silicone oil or buckle. RESULTS: After a mean follow-up of 16.8 months, 66.7% of eyes recovered better than 6/60 (20/200) vision and 75.6% had attached retina. On univariate analysis, scleral entry wound, posterior segment IOFB, larger size of IOFB, and retinal damage were found to be associated with poor anatomic outcome. Lower presenting visual acuity, hyphema, retinal damage, subretinal hemorrhage, detached retina, and larger IOFB were associated with a poor functional result. Multivariate analysis identified retinal damage caused by the foreign body as the only factor significantly associated with poor anatomic as well as functional outcome. CONCLUSIONS: Glass IOFBs are caused in a majority of cases by blast injury. Bilaterality is not uncommon. Presence of retinal damage is predictive of poor functional and anatomic results. Overall results are modest with modern vitreoretinal surgical techniques.
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Segmento Anterior del Ojo/lesiones , Cuerpos Extraños en el Ojo/cirugía , Lesiones Oculares Penetrantes/cirugía , Vidrio , Procedimientos Quirúrgicos Oftalmológicos , Retina/lesiones , Adulto , Cuerpos Extraños en el Ojo/complicaciones , Cuerpos Extraños en el Ojo/diagnóstico , Lesiones Oculares Penetrantes/complicaciones , Lesiones Oculares Penetrantes/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Cristalino/lesiones , Masculino , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/etiología , Desprendimiento de Retina/cirugía , Estudios Retrospectivos , Esclerótica/lesiones , Resultado del Tratamiento , Agudeza VisualRESUMEN
PURPOSE: Cidofovir (HPMPC) is a potent long-acting anticytomegalovirus agent. In humans, its dose-limiting intravitreal toxicity results in the lowering of intraocular pressure (IOP). The purpose of the present study was to determine the effects of HPMPC and various acyclic nucleoside phosphonate (ANP) analogues when administered intravitreally in guinea pig eyes and to establish the structural and functional relation of these compounds in connection with their effects on the ciliary body and retina. METHODS: Ninety-six guinea pig eyes were injected with various doses of HPMPC and ANP analogues. RESULTS: Severe lowering of IOP with structural alterations of the ciliary body was observed when doses were administered that achieved final intravitreal concentrations greater than 25 microg/ml HPMPC, 200 microg/ml cyclic HPMPC (cHPMPC), 25 microg/ml (S)-HPMPA, and 625 microg/ml PMEG. Concentrations of 25 microg/ml HPMPC, 200 microg/ml cHPMPC or less, and all concentrations of (R)-HPMPA, HPMPU, PMEA, PMEC, PMEDAP, (R)-PMPA, and (S)-PMPA did not lower IOP significantly, nor did they cause significant histologic changes. CONCLUSIONS: Of the HPMP series, the cyclic analogue of HPMPC (cHPMPC) and HPMPC are the least toxic of the compounds that show potent anti-human cytomegalovirus activity (HCMV). PMEG, the most potent anti-HCMV compound of the PME series, is toxic at higher doses. Further evaluation of lower doses is needed. Compounds of the PMP series are not toxic, but they show no anti-HCMV activities. The IOP-lowering effect of these compounds appears to be associated with an effect on the ciliary body.
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Antivirales/farmacología , Cuerpo Ciliar/efectos de los fármacos , Citosina/análogos & derivados , Presión Intraocular/efectos de los fármacos , Nucleósidos/farmacología , Organofosfonatos , Compuestos Organofosforados/farmacología , Retina/efectos de los fármacos , Animales , Antivirales/química , Cidofovir , Cuerpo Ciliar/patología , Citosina/química , Citosina/farmacología , Cobayas , Inyecciones , Nucleósidos/química , Hipotensión Ocular/inducido químicamente , Compuestos Organofosforados/química , Retina/patología , Relación Estructura-Actividad , Cuerpo VítreoRESUMEN
BACKGROUND: Fluorescein and indocyanine green (ICG) angiography are both useful in the diagnosis and treatment of many retinal diseases. In some cases, both tests must be performed for diagnosis and treatment; however, performing both is time-consuming and may require multiple injections. METHODS: We designed a compact digital confocal scanning laser ophthalmoscope to perform true simultaneous fluorescein and ICG angiography. We report our experience using the instrument to perform 169 angiograms in 117 patients. RESULTS: There were no unexpected adverse effects from mixing the dyes and administering them in 1 injection. An entire examination, including fundus photography, fluorescein angiography, and ICG angiography, could be performed in 45 minutes. It was possible to study differences in fluorescein patterns by comparing identically timed frames and to find cases in which ICG or fluorescein was optimal in visualizing retinal and subretinal structures. Confocal optical sections in the depth (z) dimension allowed viewing in different planes. It was possible to overlay ICG and fluorescein images or compare them side-by-side using a linked cursor. Digital transmission of the images was also performed. CONCLUSIONS: Simultaneous ICG and fluorescein angiography can be performed rapidly, safely, and conveniently. The availability of simultaneous angiography will allow critical determination of the relative advantages and disadvantages of both types of angiography.
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Enfermedades de la Coroides/diagnóstico , Angiografía con Fluoresceína , Colorantes Fluorescentes , Verde de Indocianina , Rayos Láser , Oftalmoscopios , Enfermedades de la Retina/diagnóstico , Coroides/irrigación sanguínea , Coroides/patología , Fluoresceína , Angiografía con Fluoresceína/métodos , Fondo de Ojo , Humanos , Procesamiento de Imagen Asistido por Computador , Vasos Retinianos/patologíaRESUMEN
PURPOSE: To investigate the effect of posterior subtenon injections of corticosteroids on intraocular pressure in a variety of ocular diseases. METHODS: We retrospectively analyzed 202 consecutive posterior subtenon corticosteroid injections (148 of methylprednisolone acetate, 80 mg, and 54 of triamcinolone acetonide, 40 mg) in 63 eyes of 55 patients (26 male, 29 female; mean age +/- SD, 60.17 +/- 26.55 years). All patients had received topical or systemic corticosteroids before the injection, and no rise in intraocular pressure had been noted. Preinjection and postinjection intraocular pressure measurements were compared by two-tailed paired t test. Statistical analysis was performed separately by patient (first injection of first injected eye), by eye (first injection of each eye), and by all injections. To detect increase in intraocular pressure during follow-up, statistical analysis was performed separately 14 to 90 days, 91 to 150 days, and 151 to 270 days after injection. RESULTS: No statistically significant difference was found between preinjection and postinjection intraocular pressure measurements. A power calculation in the most stringent subanalysis (by patient) proved that there is only a 3.87% chance to statistically miss a clinically significant rise in intraocular pressure from 15 to 21 mm Hg. CONCLUSIONS: Posterior subtenon injection of corticosteroids does not cause an increase in intraocular pressure. All patients in our study had been treated previously with topical or systemic corticosteroids and did not react with an excessive increase in intraocular pressure. This safety of repository corticosteroids may therefore not apply to patients whose status in responding to corticosteroids is not known.
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Glucocorticoides/administración & dosificación , Presión Intraocular/efectos de los fármacos , Metilprednisolona/administración & dosificación , Triamcinolona/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Tejido Conectivo , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas , Estudios RetrospectivosRESUMEN
OBJECTIVE: The purpose of the study is to evaluate the adverse events and autopsy findings in a series of consecutive 20-microg intravitreous cidofovir injections at a single institution. DESIGN: The study design was a nonrandomized, consecutive case series. PARTICIPANTS: Seventy-six patients with acquired immune deficiency syndrome with cytomegalovirus retinitis were studied prospectively. Sixty-three patients had 1 month's follow-up or longer, and this comprised the study group. In addition, histopathologic findings from 18 eyes of 9 patients were studied at autopsy. INTERVENTION: A total of 296 injections of 20 microg cidofovir were given in 115 eyes. Sixty-three patients who had 246 injections in 93 eyes had 1 month's follow-up or longer for the evaluation of adverse events. MAIN OUTCOME MEASURES: Postinjection chronic hypotony associated with permanent visual loss, transient hypotony, iritis, and its long-term sequela (posterior synechia and cataract, retinal detachment, extraocular cytomegalovirus involvement) were the outcomes of interest in this study. Additionally, light and electron microscopic studies of human eyes were performed. RESULTS: The most severe adverse event was postinjection chronic hypotony. This phenomenon was associated with permanent visual loss. This was observed in 1% of the injections and 3% of the eyes of the patients (95% confidence interval, 0%-6%). Transient hypotony associated with mild-to-moderate visual loss developed in 14%, but vision recovered to baseline levels in these eyes subsequently. Analysis showed that transient hypotony in the injected eye could predict postinjection chronic hypotony in the fellow eye (two-tailed Fisher's exact test, P = 0.02). The incidence of iritis was 32%; posterior synechia and cataract were the long-term sequela of the iritis and developed in 19% and 11% of the eyes, respectively. The incidence of retinal detachment was lower (6%). Histopathologic evaluation of the eyes showed mild-to-moderate atrophy of the nonpigmented epithelium of the ciliary body and no other evidence of intraocular toxicity. CONCLUSIONS: The most serious adverse event was postinjection chronic hypotony, which occurred in 3% of eyes. Episodes of transient hypotony appear to indicate that the fellow eye was predisposed to chronic hypotony. Therefore, it may be prudent to give intravitreous injections at least 2 weeks apart in the fellow eye to evaluate the clinical response of the injected eye.
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Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antivirales/efectos adversos , Retinitis por Citomegalovirus/tratamiento farmacológico , Citosina/análogos & derivados , Iritis/inducido químicamente , Hipotensión Ocular/inducido químicamente , Organofosfonatos , Compuestos Organofosforados/efectos adversos , Adulto , Segmento Anterior del Ojo/efectos de los fármacos , Segmento Anterior del Ojo/patología , Antivirales/administración & dosificación , Autopsia , Cidofovir , Citosina/administración & dosificación , Citosina/efectos adversos , Femenino , Estudios de Seguimiento , Fondo de Ojo , Humanos , Inyecciones , Iritis/patología , Masculino , Persona de Mediana Edad , Hipotensión Ocular/patología , Compuestos Organofosforados/administración & dosificación , Epitelio Pigmentado Ocular/efectos de los fármacos , Epitelio Pigmentado Ocular/ultraestructura , Estudios Prospectivos , Cuerpo VítreoRESUMEN
OBJECTIVE: To study complications of vitrectomy surgery for full-thickness macular holes. DESIGN: A multicentered, randomized, controlled clinical trial. PARTICIPANTS: Community and university-based ophthalmology clinics. INTERVENTION: Standardized macular hole surgery versus observation. MAIN OUTCOME MEASURES: Assessment of anatomic and visual outcomes and determination of postoperative complications at 12 months after randomization. RESULTS: Posterior segment complications were noted in 39 eyes (41%). The incidence of retinal pigment epithelium (RPE) alteration and retinal detachment (RD) were 33% and 11%, respectively. One RD due to a giant retinal tear resulted in a visual acuity of light perception. Other complications included a reopening of the macular hole in 2 eyes (2%), cystoid macular edema in 1 eye (1%), a choroidal neovascular membrane in 1 eye (1%) and endophthalmitis in 1 eye (1%). Eyes with complications had significantly worse visual acuity outcomes as determined by the Early Treatment Diabetic Retinopathy Study, Word Reading, and Potential Acuity Meter charts (P < 0.01 for all comparisons). Eyes with macular holes greater than 475 microns were more than twice as likely to have complications than eyes with holes less than 475 microns (odds ratio [OR] = 2.2, P = 0.07). Before surgery, the stage of the hole was related to postoperative RPE changes (P < 0.0001) and the occurrence of postoperative RD (P = 0.0002). Intraoperative trauma was related to the occurrence of these complications (P < 0.0001 for RPE changes, P = 0.02 for RDs). Epiretinal membrane removal was related to RPE changes (P = 0.02) but not RDs. CONCLUSIONS: The RPE alterations and RDs are common after macular hole surgery and result in significantly reduced postoperative visual acuity. The RPE changes may be related to surgical trauma or light toxicity. Further efforts to reduce complications associated with macular hole surgery are indicated.
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Complicaciones Posoperatorias , Perforaciones de la Retina/cirugía , Trastornos de la Visión/etiología , Vitrectomía/efectos adversos , Anciano , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Incidencia , Masculino , Epitelio Pigmentado Ocular/patología , Epitelio Pigmentado Ocular/fisiopatología , Desprendimiento de Retina/etiología , Desprendimiento de Retina/patología , Desprendimiento de Retina/fisiopatología , Trastornos de la Visión/patología , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: To evaluate the decrease in intraocular pressure associated with cidofovir (1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate; HPMPC) intravitreal injections. METHODS: We followed up 97 eyes of 63 patients with acquired immunodeficiency syndrome (AIDS) who had cytomegalovirus retinitis and had been treated with up to nine 20-microgram intravitreal cidofovir injections. Measurements were taken at baseline, between 2 and 3 weeks, and at 5 to 6 weeks after injections. Anterior chamber fluorophotometry was studied in seven eyes (four patients) before and after injections. Ciliary body anatomy was evaluated in two patients. RESULTS: After the first intravitreal injection, mean intraocular pressure was 2.2 mm Hg lower than that at baseline at 2 to 3 weeks (P < .001) and 1.3 mm Hg lower than at baseline at 5 to 6 weeks (P = .0025). After the second injection, mean pressure was 2.6 mm Hg lower at 2 to 3 weeks (P = .0013) and 1.5 mm Hg lower at 5 to 6 weeks (P = .043). After subsequent injections, however, the decrease was less than 1 mm Hg, suggesting that a plateau had been reached. Pressure in eyes with anterior uveitis after the first injection was lower than that in eyes without anterior uveitis (P < .0001). The mean rate of aqueous flow decreased from 2.8 to 1.9 microliters per minute 2 to 4 weeks after injection (P < .015). Ultrasound biomicroscopy disclosed that severe hypotony after cidofovir injections is associated with ciliary body atrophy. CONCLUSIONS: Intraocular pressure decreases after the initial 20-microgram cidofovir intravitreal injection. However, eyes stabilize (pressure plateaus) after three injections. Effects on the ciliary body are the main cause of the decrease after cidofovir injections.
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Síndrome de Inmunodeficiencia Adquirida/fisiopatología , Antivirales/uso terapéutico , Humor Acuoso/efectos de los fármacos , Infecciones por Citomegalovirus/tratamiento farmacológico , Citosina/análogos & derivados , Presión Intraocular/efectos de los fármacos , Organofosfonatos , Compuestos Organofosforados/uso terapéutico , Retinitis/virología , Adulto , Cámara Anterior/patología , Humor Acuoso/fisiología , Cidofovir , Cuerpo Ciliar/diagnóstico por imagen , Cuerpo Ciliar/efectos de los fármacos , Infecciones por Citomegalovirus/fisiopatología , Citosina/efectos adversos , Citosina/uso terapéutico , Esquema de Medicación , Femenino , Fluorofotometría , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Compuestos Organofosforados/efectos adversos , Estudios Prospectivos , Ultrasonografía , Cuerpo VítreoRESUMEN
PURPOSE: The authors have shown that long-term treatment of cytomegalovirus (CMV) retinitis with 20-microgram intravitreal injections of cidofovir (HPMPC) is highly effective but may be associated with iritis and profound hypotony. They evaluated the efficacy and safety of 10-microgram intravitreal injections of cidofovir and made comparisons with their findings of 20-microgram injections. METHODS: The current study was conducted as a nonrandomized consecutive case series at the AIDS Ocular Research Unit of the University of California at San Diego. Twenty-seven eyes of 18 patients were injected with 10 micrograms intravitreal cidofovir and had complete follow-up. These were compared with another consecutive series of 24 eyes of 17 patients injected with 20 micrograms of cidofovir. MAIN OUTCOME MEASURES: The main outcome in this study was the incidence of failure to respond to treatment with 10-microgram injections. The authors also compared the time to progression of CMV retinitis after the initial intravitreal injections of 10 micrograms and 20 micrograms of cidofovir. Secondary outcomes included incidence of iritis and changes in intraocular pressure (IOP) after cidofovir injections. RESULTS: The median time to retinitis progression was 45 days after a single intravitreal injection of 10 micrograms cidofovir compared with 55 days with the authors' series of 20-microgram injections. This difference was statistically significant (P = 0.033, log-rank test) and appeared to be due principally to a 26% incidence of primary failure in the 10-microgram group (progression > or = 750 microns within 28 days, P = 0.0017 Wilcoxon test). Progression after a second injection of 10 micrograms cidofovir was more rapid (32 days, P = 0.037). The incidence of iritis after 10-microgram injections was 2.2% compared with 23% with 20-microgram injections (P = 0.003, Fisher's exact test, two-tailed). There was less decrease in IOP between the baseline injection and subsequent visits in the 10-microgram group. CONCLUSIONS: Treatment of CMV retinitis with 10-microgram intravitreal cidofovir injection was not as effective as with 20 micrograms and may allow development of drug resistance, but there were fewer side effects with the 10-microgram dose. The drug appears to have a narrow therapeutic index, and other attempts at reducing the side effects while preserving the long-acting effect, such as liposome delivery, may be warranted.
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Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antivirales/administración & dosificación , Retinitis por Citomegalovirus/tratamiento farmacológico , Citosina/análogos & derivados , Organofosfonatos , Compuestos Organofosforados/administración & dosificación , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/patología , Adolescente , Adulto , Antivirales/uso terapéutico , Cidofovir , Retinitis por Citomegalovirus/complicaciones , Retinitis por Citomegalovirus/patología , Citosina/administración & dosificación , Citosina/uso terapéutico , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Fondo de Ojo , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Compuestos Organofosforados/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Cuerpo VítreoRESUMEN
Intravitreal cidofovir has been shown to be a long acting and highly efficacious treatment for CMV retinitis; however decrease in IOP is an adverse effect. We wanted to determine the effect of cidofovir on intraocular pressure (IOP) in the guinea pig, and rabbit eye to develop an animal model of cidofovir induced ocular hypotony and to study the histopathology of this toxicity. Twenty-eight guinea pig eyes were injected with cidofovir yielding final intravitreal concentrations of 25, 200, 625 and 2000 micrograms ml-1. Eighteen eyes of pigmented rabbits were injected with cidofovir yielding final intravitreal concentrations of 625 and 2000 micrograms ml-1. A carefully calibrated low volume displacement manometer system using a micro-transducer was used to determine the IOP measurements in the guinea pig and rabbit eyes. Histology was evaluated using light and electron microscopy. Injection of 6.25 micrograms of cidofovir intravitreally (vitreous concentration of 25 micrograms ml-1) is the highest non-toxic dose in the guinea pig; the IOP was unchanged at two and four weeks after injection with this dose; histologically the eyes were normal. A single injection of 50 micrograms of cidofovir intravitreally (vitreous concentration of 200 micrograms ml-1) caused a long lasting (9.3 mmHg) decrease in IOP (approximately 50% of baseline). At this dose there were only mild and variable histologic changes in the ciliary body and the retina. Higher doses of 156.25 micrograms and 500 micrograms of cidofovir (vitreous concentrations of 625, and 2000 micrograms ml-1, respectively) caused moderate to severe ciliary body and retinal changes. In rabbit eyes there was a mild but statistically insignificant pressure drop with doses of 875 micrograms cidofovir intravitreally (vitreous concentration of 625 micrograms ml-1); retina was within normal limits after injection with this dose, there were mild changes in the ciliary body. There was a total destruction of ciliary body and loss of nonpigmented epithelial cells with injections of 2800 micrograms of cidofovir intravitreally (vitreous concentration of 2000 micrograms ml-1): retina was relatively well preserved. The guinea pig eye shows similar reduction in IOP and ciliary body changes as are seen in the human eye after intravitreal cidofovir and also appears to have a similar dose-response curve. However, the reduction of IOP caused by cidofovir occurs in the guinea pig eye at a concentration 40 times higher than was observed in the human eye.
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Citosina/análogos & derivados , Modelos Animales de Enfermedad , Oftalmopatías/inducido químicamente , Presión Intraocular/efectos de los fármacos , Organofosfonatos , Compuestos Organofosforados/toxicidad , Animales , Cidofovir , Cuerpo Ciliar/efectos de los fármacos , Cuerpo Ciliar/patología , Cuerpo Ciliar/ultraestructura , Enfermedades de la Córnea/inducido químicamente , Enfermedades de la Córnea/patología , Citosina/toxicidad , Oftalmopatías/patología , Cobayas , Presión Intraocular/fisiología , Iritis/inducido químicamente , Iritis/patología , Microscopía Electrónica , Epitelio Pigmentado Ocular/patología , Epitelio Pigmentado Ocular/ultraestructura , Retina/ultraestructura , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/patología , Enfermedades de la Úvea/inducido químicamente , Enfermedades de la Úvea/patologíaRESUMEN
BACKGROUND: Acyclovir diphosphate dimyristoylglycerol is a lipid prodrug of acyclovir that forms liposomes and provides substantial activity against herpes simplex virus, acyclovir-resistant strains of herpes simplex virus, and human cytomegalovirus. We therefore tested this promising new drug in a rabbit model of herpes simplex retinitis. METHODS: A total of 22 pigmented rabbits were pretreated with either acyclovir diphosphate dimyristoylglycerol, ganciclovir, acyclovir, or buffer. Retinae then were inoculated with herpes simplex virus-1 or buffer 1 week after the injection of drug. In another experiment we compared the effects of acyclovir diphosphate dimyristoylglycerol and acyclovir diphosphate dioleoylglycerol on the optical clarity of vitreous. RESULTS: Animals injected intravitreally with acyclovir diphosphate dimyristoylglycerol showed retinitis that was less severe than that in animals injected with ganciclovir, acyclovir, and buffer; differences in grading scores of the retinitis between animals injected with acyclovir diphosphate dimyristoylglycerol and those injected with buffer were statistically significant (P = 0.0015). Vitreous and optical media became clear 4 days after acyclovir diphosphate dioleoylglycerol injection compared with 10 days after with acyclovir diphosphate dimyristoylglycerol injections. CONCLUSION: Acyclovir diphosphate dimyristoylglycerol had prolonged antiviral activity against herpes simplex virus-1 retinitis in a rabbit model. This drug delivery system, modified to improve optical clarity, may allow long-acting intravitreal treatment of cytomegalovirus retinitis and other retinal diseases.
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Aciclovir/análogos & derivados , Antivirales/uso terapéutico , Herpes Simple/tratamiento farmacológico , Fosfatidilgliceroles/uso terapéutico , Profármacos/uso terapéutico , Retinitis/tratamiento farmacológico , Simplexvirus , Aciclovir/uso terapéutico , Animales , Modelos Animales de Enfermedad , Ganciclovir/uso terapéutico , Herpes Simple/virología , Liposomas , Conejos , Retinitis/virología , Simplexvirus/fisiología , Replicación ViralRESUMEN
BACKGROUND: The authors developed an agar sandwich technique for retinal biopsy processing. This tissue agar embedding technique allows for a rapid and reliable method to handle and transport retinal biopsies from the operative field to the histology laboratory. METHODS: Biopsies from rabbit retinas infected with herpes simplex virus, epiretinal membranes from patients with macular pucker, and retinas from patients with acute retinal necrosis were studied. Each retinal biopsy was fixed, mounted on an agar disc, and covered with liquid agar. Light microscopy, electron microscopy, immunocytochemistry, and polymerase chain reaction were employed on the agar-embedded tissue. RESULTS: The tissues remained mounted in the agar sandwich and maintained their orientation throughout the processing. The morphologic integrity, histologic characteristics, antigenic properties, and DNA quality all were preserved using the agar sandwich technique. CONCLUSION: The agar sandwich technique is an efficient and simple technique for handling small biopsy specimens that require various analyses.
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Infecciones Virales del Ojo/diagnóstico , Herpes Simple/diagnóstico , Herpes Zóster Oftálmico/diagnóstico , Retina/patología , Síndrome de Necrosis Retiniana Aguda/diagnóstico , Retinitis/diagnóstico , Adhesión del Tejido/métodos , Agar , Animales , Antígenos Virales/análisis , Biopsia , ADN Viral/análisis , Infecciones Virales del Ojo/etiología , Herpes Simple/etiología , Herpes Zóster Oftálmico/etiología , Humanos , Técnicas para Inmunoenzimas , Mácula Lútea/patología , Reacción en Cadena de la Polimerasa , Conejos , Retina/virología , Síndrome de Necrosis Retiniana Aguda/virología , Retinitis/virología , Simplexvirus/fisiologíaRESUMEN
PURPOSE: The authors determine the intraocular tolerance of a new widely used liquid perfluorocarbon, perfluoroctylbromide (perflubron). METHODS: Pars plana vitrectomy was performed on 54 eyes of 54 patients with vitreoretinal disorders at three centers. Diagnoses included giant retinal tears, proliferative vitreoretinopathy, and dislocated intraocular and crystalline lenses. At the conclusion of the vitrectomy, perflubron was removed. RESULTS: Perflubron was efficacious for vitreoretinal manipulation. Of the 45 eyes with retinal detachment, 23 (51.1%) of the retinas were reattached after a single surgery; redetachment occurred in 22 (48.9%) after the initial procedure, and further surgery was necessary to reattach the retina. Final retinal reattachment was achieved in 40 (88.9%) eyes. Mean visual acuity improvement was six lines (P < 0.0019). Visualization of the water/perfluorocarbon interface was good. There was no evidence of adverse effects from perflubron on the retina, lens, or anterior segment. CONCLUSION: Findings indicate that perflubron is safe for temporary intraoperative use intravitreally. The absence of adverse effects is consistent with the properties of perflubron that our group has studied in the eyes of animals and in other uses in human patients.