Original article
Crystalline keratopathy secondary to the use of ciprofloxacin after cataract surgery with confirmation by histopathological study: A case report and review of the literature
Queratopatía cristalina secundaria al uso de ciprofloxacino tras cirugía de catarata con comporbación por estudio histopatológico: Reporte de un caso y revisión de la literatura
Asociación para Prevenir la Ceguera en México I. A. P., Mexico City, Mexico
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García-Uribe, M. Preciado" "autores" => array:2 [ 0 => array:4 [ "nombre" => "P.A." "apellidos" => "García-Uribe" "email" => array:1 [ 0 => "pabloangel6@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Preciado" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Asociación para Prevenir la Ceguera en México I. A. P., Mexico City, Mexico" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Queratopatía cristalina secundaria al uso de ciprofloxacino tras cirugía de catarata con comporbación por estudio histopatológico: Reporte de un caso y revisión de la literatura" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 278 "Ancho" => 805 "Tamanyo" => 33387 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A) Whitish punctate epithelial deposits in the central cornea with resolution of the epithelial defect after lubricant change. (B) Higher magnification shows better characteristics of the lesion.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Topical fluoroquinolones are widely used as broad-spectrum antibiotics after cataract surgery and have been associated with corneal deposits in epithelium and superficial stroma. A case of crystalline keratopathy secondary to topical ciprofloxacin after cataract surgery in a 75-year-old male is presented.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">Male, 75, with a history of type 2 diabetes mellitus and systemic arterial hypertension with adequate medical control, underwent phacoemulsification with intraocular lens placement in the left eye indicated for cataract stage NO2 NC2 C1 P4 (LOCS III). Postoperatively, drops with prednisolone acetate 1% Q2 h in weekly dose reduction scheme, sodium hyaluronate 4 mg/ml QID, bromfenac 0.09% BID and ciprofloxacin QID were indicated.</p><p id="par0015" class="elsevierStylePara elsevierViewall">One week later, during a routine examination the patient exhibited generalized stromal edema, central folds in Descemet’s membrane, a central circular epithelial defect staining and accumulating with fluorescein of approximately 3 × 2 mm and multiple whitish punctate deposits in the area of the lesion (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Sodium hyaluronate deposition was suspected, so the lubricant was changed to 3% trehalose with rapid steroid reduction to promote closure of the epithelial defect. After 3 days, improvement of the epithelial defect was observed, but corneal deposits persisted (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Due to the persistence of corneal deposits, surgical debridement was performed under slit lamp visualization to accelerate clinical resolution, obtain samples and perform histopathological study to determine the origin of the infiltrates. In addition, ciprofloxacin drops were discontinued and management was continued with netilmicin 0.3% and dexamethasone 1.14 mg/ml QID. Three days later, on routine examination, the patient was found to have complete dissipation of corneal infiltrates and a paracentral inferior epithelial defect (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">However, due to the irregular and fragile appearance of the epithelium despite resolution of the corneal infiltrates, the patient continued with dry eye management. At one week, complete closure of the epithelial defect and a final vision of 20/40 was observed at the follow-up appointment. The composition of the extracted material was subjected to kerosene embedding and hematoxylin-eosin staining for further microscopic examination. The final report revealed epithelial cells and basophilic particles compatible with drug precipitates (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">Topical fluoroquinolones, and in particular ciprofloxacin, are widely used as broad-spectrum antibiotics after cataract surgery and have been associated with interpalpebral corneal deposits usually described as punctate or plaque-like crystalline deposits. The latter may be caused by an epithelial defect, prolonged use of the drug, infection, corneal transplant surgery or pH-dependent decrease in solubility, which favors its precipitation on the cornea. However, ciprofloxacin crystalline keratopathy can occur in the absence of these factors.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Crystalline keratopathy secondary to topical ciprofloxacin can develop in up to 18% of patients and usually causes decreased visual acuity when the epithelium and visual axis are compromised.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Conventional management usually consists only of discontinuation of the drug and substitution with another class of antibiotic, with complete resolution of the deposits and good visual results after an average of 14 days after discontinuation of treatment. However, in cases where crystalline keratopathy persists despite drug discontinuation, debridement of the lesions<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> can be chosen, as was demonstrated in the present case. Furthermore, this maneuver made it possible to obtain a sufficient amount of tissue to perform kerosene embedding and hematoxylin-eosin staining to analyze the nature of the deposits. The histopathological report allowed us to determine that the deposits were compatible with antibiotic precipitates. Previous studies have shown that these deposits are composed of pure crystallized fluoroquinolone that is still bioactive and bioavailable, which may in part explain why these drugs have good cure rates for ophthalmic infections due to their ability to resolubilize and continue to act after application.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">After resolution of the corneal infiltrates, the patient persisted with dry eye syndrome. Most likely, his underlying pathology, along with the cataract procedure, acted as synergistic entities that facilitated ciprofloxacin precipitation. Ciprofloxacin has a pH-dependent solubility, with a significant decrease in solubility at alkaline pH. Different factors such as topical polypharmacy, changes in tear film pH, short dosing intervals, presence of harmful disinfectants such as benzalkonium chloride in topical formulations, low reflex tearing as well as inadequate tear film production and mixing as in the case of our patient, can lead to rapid precipitation and corneal deposits of antibiotic.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conclusions</span><p id="par0050" class="elsevierStylePara elsevierViewall">Topical fluoroquinolones are a group of safe and effective antimicrobial drugs that are widely used as broad-spectrum antibiotics after cataract surgery. However, they are not free of complications such as crystalline keratopathy. While there are some reports of corneal deposits with the use of ciprofloxacin as a preventive measure against postsurgical infection, there are no other case reports in which complete photographic follow-up has been shown. Also, no other publication has shown the processing, staining and microscopic examination of the specimen obtained by debridement. This case is a good example that common adverse reactions due to a drug can be easily managed by evaluating the problem step by step until diagnosis is reached. It is also important to mention that all drugs, even when administered topically and in a very specific organ, should be indicated and used prudently taking into account the risks involved.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">CRediT authorship contribution statement</span><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">P.A. García-Uribe:</span> Conceptualization, Methodology, Writing – original draft. <span class="elsevierStyleBold">M. Preciado:</span> Conceptualization, Supervision, Resources.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">No conflicts of interest were declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres2157671" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1830879" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2157672" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1830878" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusions" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "CRediT authorship contribution statement" ] 9 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2024-02-02" "fechaAceptado" => "2024-03-12" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1830879" "palabras" => array:4 [ 0 => "Crystalline keratopathy" 1 => "Ciprofloxacin" 2 => "Corneal deposits" 3 => "Topical fluoroquinolone" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1830878" "palabras" => array:4 [ 0 => "Queratopatía cristalina" 1 => "Ciprofloxacina" 2 => "Depósitos corneales" 3 => "Fluoroquinolona tópica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To report the case of a 75-year-old patient who presented crystalline keratopathy secondary to the use of topical ciprofloxacin with histopathological verification, after cataract surgery without complications.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Case report with clinical and photographic follow-up, as well as slides with samples of epithelium and crystalline deposits.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Corneal deposits resolved after drug suspension, topical lubricant change, and subsequent surgical debridement. The histopathological examination reported epithelial cells and basophilic particles compatible with drug precipitates.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Crystalline keratopathy is a condition in which crystals of various kinds are deposited in the corneal epithelium and/or in the anterior stroma. It may have an infectious, pharmacological cause or, in rarer cases, corneal dystrophies. Certain factors such as a previous epithelial defect, systemic pathology with diabetes mellitus, ocular surgery and previous dry eye can favor the deposition of ciprofloxacin leading to the formation of a keratopathy.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Reportar el caso de una paciente de 75 años que presentó queratopatía cristalina secundaria al uso de ciprofloxacino tópico con comprobación histopatológica, luego de cirugía de catarata sin complicaciones.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Método</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Reporte de caso con seguimiento clínico y fotográfico, así como laminillas con muestras de epitelio y depósitos cristalinos.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Los depósitos corneales resolvieron tras la suspensión del fármaco, cambio de lubricante tópico y desbridamiento quirúrgico posterior. El examen histopatológico reportó células epiteliales y partículas basófilas compatibles con precipitados del fármaco.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">La queratopatía cristalina es una afección en la que los cristales de diversa índole se depositan en el epitelio corneal y/o en el estroma anterior. Puede tener una causa infecciosa, farmacológica o, en casos más raros, por distrofias corneales. Ciertos factores como un defecto epitelial previo, patología sistémica con diabetes mellitus, la realización de una cirugía ocular y ojo seco previo pueden favorecer la precipitación depósito de ciprofloxacino llevando a la formación de una queratopatía cristalina.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 327 "Ancho" => 805 "Tamanyo" => 43747 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Whitish punctate deposits in the cornea associated with epithelial defect. (B) Fluorescein staining under blue filter showing the epithelial defect.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 278 "Ancho" => 805 "Tamanyo" => 33387 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A) Whitish punctate epithelial deposits in the central cornea with resolution of the epithelial defect after lubricant change. (B) Higher magnification shows better characteristics of the lesion.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 279 "Ancho" => 805 "Tamanyo" => 37631 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(A) Epithelial defect secondary to debridement. (B) Secondary epithelial defect delineated with fluorescein stain and blue light filter.</p>" ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 334 "Ancho" => 805 "Tamanyo" => 55033 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">(A) Photomicrograph of corneal epithelium with hematoxylin and eosin staining. These are cells of the corneal epithelium with basophilic particles compatible with drug precipitates. 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