| PurposeThere are no standardized protocols or guidelines for the treatment of recurrent fungal keratitis after therapeutic keratoplasty.This study aimed to investigate the incidence of recurrent fungal keratitis after the primary keratoplasty and the visual outcome and prognosis after intervention for the recurrence.MethodsThis was a retrospective study.From January 2004 to December 2015,1448 patients with fungal keratitis(FK)were treated with therapeutic keratoplasty at Shandong Eye Hospital Qingdao Eye Hospital.112 patients(112 eyes)with recurrent fungal keratitis after therapeutic keratoplasty were studied.Recurrent fungal keratitis was diagnosed by clinical examination(e.g.,gray-white invasive lesion of the recipient bed,mushroom-shaped pus mass at the anterior chamber angle,pus mass at the pupillary zone,and/or hypopyon reappearance)or confocal microscopy that was used to confirm the presence of fungal hyphae deep in the cornea.Etiologic diagnosis was based on fungal hyphae-positive smears or fungal culture from specimens obtained during secondary surgery.The recurrent fungal patients were classified as recipient bed recurrence,anterior chamber recurrence,posterior segment recurrence andby and atypical recurrence by determining different initial recurrence sites based on the clinical featuresGray-white invasive lesion of the recipient bed including the donor/host junction was the main clinical feature of recipient bed recurrence patients.Some patients may have purulent exudate at the donor/host junction,or additional hypopyon.Isolated white mushroom-shaped pus mass at the anterior chamber angle or the surface of the iris was the main clinical feature of anterior chamber recurrence patients.Pus mass at the pupillary zone was the main clinical feature of posterior segment recurrence patients.The pus mass at the pupillary zone suggests that the initial recurrence site is at the posterior segment.The pus from the posterior segment crosses the pupil into the anterior chamber and forms a pus mass at the pupillary zone.And vitreous opacity by B-ultrasound examination would be obtained then.Hypopyon without invasive lesion of the recipient bed,mushroom-shaped pus mass,or pus mass at the pupillary zone was the main clinical feature of atypical recurrence patients.Recurrence of fungal keratitis was also classified as early recurrence(occurring within 8 days after therapeutic keratoplasty)or late recurrence(occurring from 2 weeks after therapeutic keratoplasty)The general treatment for recurrent fungal infection was aggressive medical therapy.All patients received antifungal drugs both topically(0.5%fluconazole or voriconazole drops every 15 min combined with 0.25%amphotericin B or 5%natamycin drops once every hour)and subconjunctivally(injections of 3 mg fluconazole or voriconazole once or twice daily).For some patients with recipient bed recurrence,intrastromal injections of antifungal drugs(1 mg fluconazole or voriconazole once or twice daily)were initially conducted.Individualized treatment was conducted if the general treatment was ineffective after 3-5 days of treatmentrecipient bed recurrencea.PK with the same diameter of LK for deep RBC under the lamellar graft after initial LK.b.Corneal lesion resection+bulbar conjunctiva flap covering for superficial peripheral RBC after initial LKc.PK with expanded diameter of LK for deep peripheral RBC after initial LK.d.Expanded diameter of PK for RBC involving the corneal graft after initial PK.e.Corneal lesion resection for RBC<2 mm and not involving the corneal graft after initial PK;expanded diameter of PK for uncontrolled recurrence after resection.f.Expanded diameter of PK for RBC>2 mm and not involving the sclera after initial PK.g.PK with patch graft for RBC>2 mm involving slightly the sclera after initial PK.h.Enucleation or evisceration for widespread infection of the sclera after initial PK.anterior chamber recurrenceRemoval of mushroom-shaped pus mass and anterior chamber injection of 0.1 mg fluconazole or voriconazole once daily were the first choice;If these measures fail to control infection then anterior chamber lavage and complete removal of recurrent lesions were conducted.posterior segment recurrenceRemoval of the pus mass at the pupillary zone and antifungal drugs for the anterior chamber lavage were often the first choice.Extracapsular lens extraction would be performed for lens infection;When the anterior vitreous was infected,intravitreal injection of 0.1 mg fluconazole or voriconazole,or 5 μg amphotericin B would be performed.And vitrectomy should be performed if the above treatments were ineffective.Enucleation or evisceration was performed for panophthalmitis.atypical recurrenceAnterior chamber lavage and exploration;resection of the recurrent site;corresponding treatments as described above for different sites and involved areas;enucleation or evisceration for widespread sclera and intraocular infection.Follow-upAll patients were followed at 1,2,and 3 months after discharge,and then every 6 months for 2 years.Best corrected visual acuity(BCVA)was assessed using comprehensive refractometry and vision chart.Recurrence was also recorded.Treatment evaluationFor the analysis of treatment effect,good prognosis was defined as the presence of visual acuity.Poor prognosis was defined as failure in infection control with evisceration or enucleation of the eyeball or termination of treatment due to ineffectiveness.Statistical analysisStatistical comparisons were conducted using SPSS 17.0(IBM,Armonk,NY,USA).Continuous variables are expressed as means ± standard deviations(SD)and were compared between groups using the Student’s t test.Categorical variables are presented as frequency and percentage and were compared between groups using the chi-square test or Fisher exact test.Two-sided P-values<0.05 were considered statistically significant.ResultsDuring the study period,1448 patients with fungal keratitis that could not be controlled medically underwent PK(937/1448,64.7%)or LK(511/1448,35.3%).Recurrent fungal keratitis occurred in 112(7.7%)of the 1448 patients treated with therapeutic keratoplasty.These 112 patients(including 81 post-PK and 31 post-LK)were included in the final analysis.Patient age ranged from 12 to 80 years(mean of 49.1 years).There were 64 men and 48 women.Seven(6.3%)of the 112 patients had treatment terminated due to ineffectiveness and 12(10.7%)of the 112 patients underwent evisceration or enucleation of the eyeball because of uncontrollable infection.The overall good p)gnosis rate for the treatment of recurrent fungal keratitis was 83.0%(93/1 12).There was no significant difference in the microbiological results between the fungal keratitis group(n=1448)and the recurrence group(n=112).There was also no significant difference in the microbiological results between the good prognosis group(n=93)and the poor prognosis group(n=19).However,the proportion of Aspergillus in patients with fungal recurrence after LK was significantly higher than that in patients with fungal recurrence after PK(P=0.008).The good prognosis rates of the different sites of recurrent fungal keratitis were:recipient bed recurrence,64/69(92.8%);anterior chamber recurrence,14/14(100%);posterior segment recurrence,1 0/16(62.5%);and atypical recurrence,5/13(38.5%).There was no significant difference in the timing of recurrence between the good and poor prognosis groups(P=0.518).The good prognosis rate of patients with recipient bed recurrence was significantly higher than that of patients with posterior segment recurrence(P<0.01)and those with atypical site recurrence(P<0.01).The good prognosis rate of patients with anterior chamber recurrence was significantly higher than that of patients with posterior segment recurrence(P=0.019)and those with atypical recurrence(P<0.01).There was no significant difference in the good prognosis rate between recipient bed recurrence and anterior chamber recurrence(P>0.05);there was no significant difference in the good prognosis rate between posterior segment recurrence and atypical recurrence(P>0.05).There was no significant difference in the rate of good prognosis between early recurrence group and late recurrence group(P=0.51 8).The recurrence rates did not differ significantly between initial PK(81/937,8.6%)and LK groups(31/511,6.1%;P=0.079),but the good prognosis rate of post-LK recurrent patients(30/31,96.8%)was significantly higher than that of post-PK recurrent patients(63/81,77.8%;P=0.017).The only recurrent site of fungal keratitis after LK was the recipient bed.Post-LK recurrent fungal keratitis occurred in the deep central bed in 25 out of 31 patients(80.6%).All patients with deep lamellar recurrence had different degrees of anterior chamber response and 68.0%of patients(17/25)had a hy opyon or severe fibrinous effusion.Of the 31 patients with post-LK recurrent fungal keratitis,8(25.8%)had a good prognosis with antifungal drug therapy(including intrastromal injections and intracameral injections),21(67.7%)were cured by PK,and one(3.2%)finally required enucleation of the eyeball due to precipitously deteriorating conditionPost-PK recurrent fungal infection occurred at various sites:recipient bed(69/81,85.2%),anterior chamber(14/81,17.3%),posterior segment(16/81,19.8%),and atypical recurrence(13/81,16.0%).After aggressive individualized treatment,63 patients(63/81,77.8%)had good prognosis;7 patients(8.6%)had treatments terminated,and 11 patients(13.5%)finally required enucleation or evisceration of the eyeball.In the good prognosis group,BVCA was well maintained during the 2 years of follow-up.ConclusionsIn conclusion,different keratoplasty approaches and different infection sites are associated with different prognoses.Recurrent fungal keratitis might require an individualized therapy tailored to the site of recurrent fungal keratitis,such that good prognosis can be achieved in the majority of patients with adequate BCVA.Further research is needed to confirm and expand the findings of the present study,with the aim of developing a standardized protocol for the management of recurrent fungal keratitis after therapeutic keratoplasty. |
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