ABSTRACT
ABSTRACT This study aims to describe a challenging clinical case of a patient with a neurotrophic and exposure corneal ulcer. A 75-year-old male patient, with history of right eye (RE) limbic stem-cell insuficiency due to complications of recurrent herpetic keratitis, underwent successful limbic stem-cell transplantation in 2008. In 2010, an uneventful penetrating keratoplasty was performed. After a cataract phacoemulsification surgery with intraocular lens implantation done in 2011, best corrected visual acuity was 20/20, and remained stable until 2015. In July 2015, the patient developed right facial nerve palsy and two months later, presented with an extensive central corneal ulcer, with a significant thinning of central stroma, without infection signs, but with an imminent risk of perforation. Treatment with topical ofloxacin and intensive ocular lubrification was started in association with permanent ocular oclusion. Due to lack of any clinical improvement, treatment with RGTA [Poli (carboximetilglucose) sulfate, dextrano T40] (Cacicol®, Thea) was started. After two weeks of treatment, a complete reepithelization and partial stromal filling was observed. Continued monitoring and treatment with artificial tears was maintained, with no recurrence observed. There is an unmet need for a medical therapy that could help corneal neurotrophic ulcers to heal. The presented clinical case shows that the approach of targeting extracellular matrix can be effective in the reepithelialization of neurotrophic and exposure corneal ulcer that do not respond to conventional treatments.
RESUMO Este trabalho relata um caso clínico desafiante de doente com uma úlcera de córnea neurotrófica e de exposição. Doente do sexo masculino, de 75 anos, com antecedentes de queratites herpéticas de repetição no olho direito (OD), complicadas com o desenvolvimento de uma insuficiência límbica, foi submetido com sucesso a transplante de células límbicas em 2008. Em 2010 foi submetido a queratoplastia penetrante e em 2011, após realização de cirurgia de catarata, apresentava uma melhor acuidade visual corrigida (MAVC) de 20/20. A MAVC manteve-se estável até Julho de 2015, altura em que desenvolveu paresia facial periférica à direita. Dois meses depois, o doente desenvolveu uma úlcera de córnea central extensa, com adelgaçamento significativo do estroma central, sem sinais de infeção, mas com risco iminente de perfuração. Foi iniciado tratamento tópico com ofloxacina, lubrificação intensiva e oclusão ocular contínua. Por ausência de melhoria clínica, foi iniciado tratamento tópico com um RGTA [Poli (carboximetilglucose) sulfato, dextrano T40] (Cacicol®, Thea). Após duas semanas de tratamento, observou-se uma reepitelização completa e regeneração parcial do estroma. Foi mantida monitorização regular e tratamento com lágrimas artificiais, sem recidiva do quadro clínico. Há uma grande necessidade de tratamentos médicos que possam ajudar na regeneração de úlceras de córnea neurotróficas e de exposição. O caso clínico apresentado sugere que os fármacos que têm por alvo a matrix extracelular poderão ser eficazes na reepitelização de úlceras de córnea neurotróficas e de exposição que não respondem ao tratamento convencional.
Subject(s)
Humans , Male , Aged , Regeneration/drug effects , Corneal Ulcer/drug therapy , Glycosaminoglycans/administration & dosage , Ophthalmic Solutions/administration & dosage , Stimulation, Chemical , Wound Healing , Administration, Topical , Dextrans/administration & dosage , Hypesthesia , Anti-Infective Agents/administration & dosageABSTRACT
Background Local medical treatment of refractory immunologic keratitis is unsuccessful,and systemic steroids and immunosuppressive agents could cause severe side-effects.Tacrolimus is a potent immunosuppressive drug,it has been proved that topical application of tacrolimus could reduce immunologic inflammation.The safety and efficacy of 0.05％ tacrolimus eye drops for refractory immunologic keratitis has not been described.Objective This study was to evaluate efficacy and safety of 0.05％ tacrolimus eye drops for refractory ulcerative keratitis.Methods A retrospective study was performed.Twenty-one eyes of 17 patients with refractory immunologic keratitis,which had uncontrolled inflammation despite initially treatment including topical steroids and 1％ cyclosporine A,were enrolled,including 11 males and 6 females,with the mean ages of 52 years.Infectious ulcer was excluded by laboratory tests.No systemic disease was found in 11 patients,and Wegener's granulomatosis,rheumatoid arthritis and ulcerative colitis were seen in 1 patient,4 patients and 1 patient respectively before presentation and they were all in remission under conventional systemic therapy.Four patients got binocularly involved and thirteen patients were monocularly involved.Of the 21 eyes,2 eyes with ulcer were ≥ 3 quarters of the limbus,and 19 eyes with ulcer were ≤ 2 quarters.All patients were treated with 0.05％ tacrolimus eyedrops after discontinuing cyclosporine A.The dosage was adjusted according to the severity of inflammation and was gradually tapered when improvement occurred.The corneal lesions were examined under the slit lamp microscope and Heidelberg HRT3 Rostock Cornea Module regularly,and inflammatory cell infiltrations were analyzed with Cell Count(R) software (Heidelberg Engineering GmbH).The safety variables were monitored regularly,including adverse response of eye,tacrolimus blood concentrations measured by chemiluminescent microparticle immunoassay (CMIA) and laboratory examinations of blood routine,blood glucose level,liver and kidney function.Results The patients were treated and followed-up for a mean duration of 18.1 months (range,8-24 months).Corneal ulcer area was obviously reduced 1 month after treatment in 19 eyes,and 2 eyes of 2 cases received anterior lamellar keratoplasty due to progressive corneal destruction despite of tacrolimus therapy.Corneal ulcer was cured 3 months after treatment,and stromal edema and infiltration disappeared 6 months after treatment under the slit lamp microscope.The inflammatory cell densities at lesion zone were (958±329),(858±339),(459±261),(192±124),(98±52),(44±24) and (3±2)/mm2 before treatment and 1 week,1 month as well as 3,6,12,24 months following treatment,respectively,showing a gradually decline as time lapse (F =125.439,P =0.000),and the inflammatory cells were significantly decreased in 1,3,6,12 and 24 months following the administration of 0.05％ tacrolimus eye drops in comparison with that before treatment (all at P =0.000).The therapy duration was 12 months in 9 eyes and 24 months in 12 eyes.Transient irritation sensation occurred in 4 eyes during the treating period.Blood concentrations of tacrolimus were below 1.0 ng/ml in all of the patients.No abnormality was found in laboratory tests.Conclusions The use of 0.05％ tacrolimus eye drops is a safe and effective approach to refractory immunologic keratitis.