Purpose
To evaluate the efficacy of corneal debridement in the treatment of clinically diagnosed cases of microsporidial keratoconjunctivitis.
Design
Prospective, double-masked randomized clinical trial.
Methods
Patients with clinical features such as multifocal, coarse, raised, punctate, round to oval epithelial lesions in the cornea in slit-lamp examination with mild to moderate conjunctival congestion, suggestive of microsporidial superficial keratoconjunctivitis, were included in the prospective study. All patients were randomized into 2 groups. Group 1 patients underwent debridement with the help of a sterile #15 blade on a Bard-Parker handle, whereas only conjunctival swabs were taken from Group 2 patients. All patients were treated with ocular lubricants.
Results
One hundred and twenty patients with clinical features suggestive of microsporidial superficial keratoconjunctivitis were included in the study. The mean age was 34.3 ± 13.6 years (Group 1) and 35.8 ± 16.2 years (Group 2) ( P = .59). The mean duration of symptoms was 6.8 ± 3.9 days (Group 1) and 7.2 ± 4.6 days (Group 2) ( P = .61). Baseline characteristics showed no difference between the 2 groups. The primary outcome was the time from the presentation to complete resolution (ie, absence of corneal lesions) of the clinical signs and symptoms. The secondary outcomes were final visual acuity and residual corneal side effects and/or scarring, if any. The mean resolution time of the corneal lesions was 5.7 ± 4.0 days (Group 1) and 5.9 ± 3.9 days (Group 2) ( P = .83). There was no significant difference in final visual outcome in the 2 groups. No serious side effects were observed.
Conclusion
Debridement does not have any significant advantage in terms of resolution of the corneal lesions and final visual outcome in cases of microsporidial keratoconjunctivitis.
Earlier considered a disease of immunocompromised patients, microsporidial keratoconjunctivitis has come to be known as a common ocular infection in large numbers of immunocompetent patients. The patients usually present with complaints of redness, photophobia, irritation, watering, and defective vision. The disease is diagnosed by clinical features and microbiological investigations. A number of clinical and in vitro studies have demonstrated variable responses of microsporidia to various therapeutic agents. However, their efficacy still remains controversial.
More recent studies and clinical observations at this institute have suggested that microsporidial keratoconjunctivitis is a self-limiting infection that does not require any specific chemotherapeutic intervention. Surgical intervention in the form of diagnostic and therapeutic debridement may help in faster clinical resolution by decreasing the microbial load in the corneal epithelium. However, there is no evidence that debridement alone helps in early resolution. It is also believed that debridement may cause stromal penetration of the organism and increase the risk of secondary infection, although there are no reports of stromal keratitis following debridement of lesions. The present study was designed to evaluate the efficacy of corneal debridement in the treatment of keratoconjunctivitis caused by microsporidia and also to determine its side effects, if any.
Patients and Methods
This single-center, double-masked randomized clinical trial examined 120 patients. The prospective study has been approved by the Institutional Review Board, L. V. Prasad Eye Institute, Hyderabad Eye Research Foundation, and registered with the Clinical Trials Registry (India) (No. CTRI/2011/11/002132). It was conducted at the L. V. Prasad Eye Institute, Bhubaneswar, India. Informed written consent was obtained from each participant before inclusion in the study. Patients were prospectively recruited between July 2011 and August 2012.
Inclusion and Exclusion Criteria
Patients presenting with clinically diagnosed superficial epithelial microsporidial keratitis or keratoconjunctivitis having a minimum of 10 discrete epithelial or subepithelial lesions at presentation were included in the study. Informed consent was taken from all patients included in the study. The exclusion criteria included clinically diagnosed cases of superficial microsporidial keratoconjunctivitis with fewer than 10 discrete lesions and/or presence of stromal infiltrates at presentation.
Patients who adhered to a follow-up visit schedule either on day 5 ± 2 days or who resolved before that day were included in the analysis. We decided on this criterion based on our previous publication, where resolution time was 5 ± 2 days.
Sample Size, Randomization, and Masking
A computer-generated randomization number was assigned to each patient at the time of initiation of treatment. As this was a double-masked study, both the study participants and the evaluating ophthalmologists were masked to the information regarding the participants undergoing debridement/conjunctival swab or otherwise. The evaluating ophthalmologists were not informed about the assigned treatment group of the patient. Another ophthalmologist who was not involved in the evaluation process during follow-up visits of the patients did debridement or took conjunctival swabs. Conjunctival swabs were taken to mask the patient.
A sample size of 36 in each group was considered sufficient to detect a difference of at least 2 days between the means of the 2 study groups and the standard deviations of 3 days in each of the 2 study groups with 80% power and 5% level of significance.
Primary and Secondary Outcome Measures
The primary outcome was the time from the presentation to complete resolution of the clinical signs and symptoms. Resolution was defined as absence of corneal lesions. The secondary outcomes were final visual acuity and residual corneal side effects and/or scarring, if any.
Procedures
At the baseline (ie, day 0), demographic information and detailed medical history were obtained from each patient. Visual acuity was measured using a Snellen chart, and slit-lamp examination was performed on all patients. All patients who exhibited clinical features of microsporidial keratoconjunctivitis, such as diffuse, multifocal, coarse, raised, punctate, round to oval epithelial lesions in the cornea, in slit-lamp examination were randomized into 2 groups.
Debridement of all the lesions was done with the help of a sterile no. 15 blade on a Bard-Parker handle (Sharp Edge Industries, Ahmedabad, India) for patients in the debridement group after instillation of topical anesthetic (0.5% proparacaine hydrochloride) eyedrop. The scraping was smeared on 2 glass slides and was subjected to direct smear examination after being stained with 10% potassium hydroxide with 0.1% calcofluor white (fluorescence microscopy) and Gram or Giemsa or modified Ziehl-Neelsen stain (1% H 2 SO 4 ). Microscopic slides were examined for all patients except 1 (inadequate sample). The corneal scraping was also inoculated onto 1 culture medium (chocolate agar/blood agar), which was incubated at 37 C for 2 weeks. A sample for polymerase chain reaction (PCR) was collected from all patients. After corneal scrapings were sent for microbiological investigation, the remaining epithelial lesions and surrounding epithelium were removed with help of a no. 15 blade. In general, epithelium surrounding the corneal lesions is relatively loose. The conjunctival sample was taken from the lower fornix with the help of a rayon swab after instillation of topical anesthetic (0.5% proparacaine hydrochloride) eyedrop for patients in the nondebridement group. Corneal scrapings and conjunctival swabs were subjected to PCR for microsporidia. PCR analysis was done using a previously described small subunit rRNA-based panmicrosporidian PCR that would amplify all medically important species of microsporidia.
All patients were prescribed artificial tear substitute, 4 times a day, and were examined on day 0, day 3 ± 1, and day 7 ± 1, and at weekly intervals until resolution of clinical signs and symptoms. Assessment of patients on follow-up visits was done by an ophthalmologist masked to the treatment.
Statistical Analysis
Baseline characteristics were compared using unpaired t test. The χ 2 test was used to compare proportions. To compare the time for resolution and intergroup visual acuity in both the groups, unpaired t test was used.
Results
Patient Disposition and Demographics
One hundred and twenty eyes of 120 patients (debridement group, 58; nondebridement group, 62) were recruited. Baseline characteristics (age, sex, duration of symptoms, clinical features) showed no relevant difference between the 2 groups ( Table 1 ). A flow chart detailing disposition of patients with microsporidial keratoconjunctivitis who were included in the clinical trial is shown in the Figure . Patients who had adhered to the scheduled follow-up visits and had corneal lesions resolved were included in the outcome analysis (ie, resolution time, scar, final visual acuity) (debridement group, 35; nondebridement group, 35). None of the study patients were immunocompromised in either group.
| Debridement Group (n = 58) | Nondebridement Group (n = 62) | P Value | |
|---|---|---|---|
| Age (y) | .59 | ||
| Mean (SD) | 34.3 (13.6) | 35.8 (16.2) | |
| Range | 16-69 | 8-77 | |
| 95% CI | 30.7-37.9 | 31.7-39.9 | |
| Sex (male:female) | 51:7 | 45:17 | .06 |
| Eye (right:left) | 28:30 | 29:33 | .98 |
| Duration of symptoms | .61 | ||
| Mean (SD) | 6.8 (3.9) | 7.2 (4.6) | |
| Range | 2-15 | 2-30 | |
| 95% CI | 5.8-7.8 | 6.9-8.4 | |
| Number of corneal lesions (>20) | 38 | 43 | .80 |
Microbiological results
Microsporidial spores were demonstrated in direct microscopic examination by 1 or more staining methods in 54 out of 57 corneal scrapings (94.7%) from the debridement group. In this group the microsporidial DNA was detected in corneal scrapings of 54 out of 58 cases (93.1%). On the other hand, PCR for microsporidial DNA was positive from conjunctival swabs in 43 of 62 cases (69.3%) in the nondebridement group.
Efficacy of Debridement
Resolution of corneal lesions
We defined resolution time as the time required for the corneal epithelial infiltrates to disappear completely (no infiltrates visible on slit-lamp examination). The mean time taken to resolve was 5.7 ± 4.0 days and 5.9 ± 3.9 days in the debridement and nondebridement groups, respectively ( P = .83) ( Table 2 ). A total of 67.5% (27/40) and 64.3% (27/42) of cases resolved within 1 week of presentation in the debridement and nondebridement groups, respectively ( P = .94) ( Figure ).
