Research Article

Early Therapeutic Keratoplasty for Acanthamoeba Keratitis

by Sérgio Kwitko1,2, Samara Barbara Marafon1,2*, Lucas Kwitko3, Diane Ruschel Marinho1,2,4

1Hospital de Clínicas de Porto Alegre, RS, Brazil

2Oftalmocentro, Porto Alegre, RS, Brazil

3Pontifícia Universidade Católica de Porto Alegre (PUC-RS), RS, Brazil

4Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

*Corresponding authors: Samara Barbara Marafon, Hospital de Clinicas de Porto Alegre, 2350 Ramiro Barcelos, Brazil.

Received Date: 08 June 2024

Accepted Date: 18 June 2024

Published Date: 20 June2024

Citation: Kwitko S, Marafon SB, Kwitko L, Marinho DR (2024) Early Therapeutic Keratoplasty for Acanthamoeba Keratitis. Ophthalmol Res Rep 8: 161. https://doi.org/10.29011/2689-7407.100161

Abstract

Purpose: To describe the findings, recurrence rate and complications following therapeutic penetrating keratoplasty (PK) in eyes with Acanthamoeba keratitis (AK). Methods: A retrospective study comparing eyes that underwent surgery in the early stages of the disease versus eyes that had surgery delayed for more than five months of disease. Results: The study analyzed 23 eyes with similar demographic characteristics. Seventeen eyes (73.91%) underwent early surgical procedures within five months (Group 1), and 6 (26.08%) had the late PK after five months (Group 2). The mean clinical treatment time between the first symptoms and surgical procedure was 1.80 + 0.915 months in group 1 and 7.83 + 2.48 months in group 2 (p < 0.001). Patients in Group 1 achieved a final mean Best-corrected visual acuity (BSCVA) of logMar 0.61 + 1.07 versus 0.98 + 0.85 in Group 2 (p =0.416). Recurrence of the AK infection occurred in 11.8% (2/17) of the early PK group and in 50% (3/6) of the eyes that underwent a late therapeutic PK (p = 0.051). Cornea rejection was the most reported complication following PK, and it affected 35.3% (6/17) of the eyes in Group 1 versus 66.7% (4/6) of the eyes in Group 2 (p = 0.183). Secondary glaucoma affected 17.6% (3/17) of patients who have undergone early PK versus 66.7% (4/6) of the eyes where surgery was delayed (p = 0.025). Conclusions: Early therapeutic PK for Acanthamoeba keratitis might have beneficial results concerning the cure of infection, fewer complications, and better visual acuity recovery than a late one.

Keywords: Keratoplasty; Acanthamoeba keratitis; Cornea infection.

Introduction

Acanthamoeba keratitis (AK) is a potentially sight-threatening corneal infection caused by a protozoan, whose most related risk factors are contact lens use and incorrect cleaning routine for the lenses [1]. The amoeba has two stages: the actively motile trophozoite stage - in charge of feeding and reproduction, and a cyst stage, which can survive long periods in unfavorable environmental conditions. Because of those variations in its stage, the treatment of AK is very challenging.

Conventional treatment for Acanthamoeba keratitis consists of triple antimicrobial administrations of tropical biguanide, diamidine, and chlorhexidine. The clinical treatment is often very long, despite the advances in antimicrobial therapy, because the cystic form is highly drug-resistant and may persist for months. It also might be influenced by the delay in diagnosis or previous misdiagnosis, as well as the high pharmacological resistance of the protozoan [2]. Furthermore, it often partially treats the pathology, resulting in vision-threatening sequelae, such as epithelial defects, corneal neovascularization, leukoma, limbal cell deficiency, expansion of the infiltrate to the limbus or sclera [3,4]. When clinical treatment fails, the surgical approach of a therapeutic keratoplasty might be an option. It has been shown that about 15.85% of the patients required curative surgery [5]. The PK performed for therapeutic purposes might remove the contaminated area before the amoeba spreads deeply to the tissue and anterior chamber. However, the perfect timing for keratoplasty, if the clinical treatment has failed, is still in debate.

Some authors have shown better results when surgery is performed in the early stages of infection, whereas others defend the idea that the surgical intervention must be postponed as much as possible [2-4,6]. When surgery is performed, the area of the graft must be large enough to remove the infection and guarantee at least a 1mm rim free of disease. If earlier, it is more likely to achieve this with the donor tissue placed into a relatively undamaged and hence non-compromised recipient bed. On the other hand, when surgery is delayed, the extension of the disease might be difficult to define. In the literature, there’s a suggested cut-off of 5 months to classify the surgical treatment as an early or late one, according to the time between symptoms and the surgery [4]. In our practice, it seems that patients who have undergone therapeutic keratoplasty in early stages following ineffective drug therapy had better outcomes than the ones who have had the therapeutic keratoplasty postponed. This study aims to analyze patients with AK treated with therapeutic keratoplasty in our department to study the infection cure rate, as well as visual effects and complications, and to seek any difference regarding the time-point of the surgery. 

Methods

A retrospective cohort to analyze the patients with AK who underwent penetrating keratoplasty (PK) for therapeutic reasons. It included patients from the public system of Hospital de Clinicas de Porto Alegre and a private clinic Oftalmocentro, Porto Alegre, Brazil, between January 1998 and December 2022. The criteria for patients eligible for PK following AK was a failed clinical treatment in patients with a positive corneal scraping or biopsy for Acanthamoeba keratitis. The failure of clinical treatment was defined as the absence of clinical response or progression of the disease despite topical treatment, including at least, but not limited to, topical biguanide, propamidine and chlorhexidine. Patients with previous ocular infections of other causes, pregnant women, and patients with follow-ups shorter than six months were excluded.

Patients were divided into two groups according to the time, in months, from symptoms to PK. Group 1 included patients undergoing PK within five months of symptoms’ onset. Group 2 includes patients who had symptoms for more than 5 months before the PK. This study was carried out in accordance with the principles of the Helsinki Declaration after receiving approval from the Health Research and Ethics Committee of the Hospital de Clinicas de Porto Alegre (GPPG-HCPA 2023-0352). All patients provided written informed consent before the procedure.

Surgical Technique

The surgery was performed either by a trained surgeon (S.K and D.M.) or by an in-training surgeon supervised by the trained ones, under peribulbar blockage or general anaesthesia in the Operation Room (OR).  The trephination size was defined intraoperatively, targeting 1mm without corneal infiltration. The diameter of the donor graft was 0.5 mm larger than the recipient trephination size, and it was fixed with 16 interrupted 10-0 nylon sutures. During the postoperative period, patients kept the anti-amoeba treatment associated with topical medications: 3 mg/mL gatifloxacin (Zymar®, Allergan, Brazil) eye drops, and 10 mg/mL prednisolone (Pred-Fort®, Allergan, Brazil) QID for seven days, which was tapered off thereafter, and 0.5 mg/mL carboxymethylcellulose (Fresh-Tears®, Allergan, Brazil) as needed.

Preoperative and Postoperative Evaluations

The primary outcome was the success rate in treating the AK without recurrence in the postoperative evaluation. Clinical manifestations of postoperative recurrence include greyish-white infiltration of the recipient or donor bed with or without stroma’s ring infiltration, anterior chamber inflammation, graft edema, and keratic precipitate. The secondary outcomes, which were evaluated at every postoperative visit, included the following:

a) Secondary glaucoma: defined as intraocular pressure above 21 mmHg, and/or glaucomatous visual field loss, and/or progression of cup/disc ratio;

b) Corneal endothelial rejection: defined as cornea edema and Descemet folds, associated with keratic precipitate and/or Khodadoust line in the absence of recurrence signs;

c) Best spectacle-corrected visual acuity (BSCVA): evaluated in the pre-operative and the last postoperative visit;

d) Demographic data.

Statistical Analysis

The data were entered into Excel and exported into SPSS v. 29.0 (SPSS / IBM, Inc., Chicago, IL, USA). BSCVA was converted to the logarithm of the minimum angle of resolution (logMAR) units for the statistical analyses. Frequencies and percentages described categorical variables, and quantitative variables were described by means and standard deviations. Kolmogorov-Smirnov test was used to evaluate the normality of the variables. An Independent T-test was used to compare the preoperative and postoperative measurements and the change differences between the two groups, and the Spearman’s rho correlation was used to analyze the variables involved in the recurrence rates. The level of statistical significance was set at P < 0.05.

Results

Twenty-three patients met the inclusion criteria. The study analyzed 23 eyes in a population of 13 female (56.5%) and ten male (43.5%) subjects. There were 17 eyes (73.91%) that underwent early surgical procedures within five months (Group 1), and 6 (26.08%) in the late PK group (after five months) (Group 2). The mean age was 40.24 + 10.59 years in group 1 and 31.83 + 14.47 years in group 2 (p = 0.072), and there were no differences in the demographic characteristics between groups (Table 1).

Group 1 PK within 5 months  (n=17)

Group 2 PK after 5 months (n=6)

P value

Gender, female

9 (52.9%)

4 (66.7%)

0.5601

Eye, right

9 (52.9%)

3 (50%)

0.9011

Age (years)

40.24 + 10.59

31.83 + 14.47

0.0722

pre-BSCVA (logMAR)

2.04 ± 0.16

1.83 ± 0.80

0.5552

Table 1: Demographic data;PK = therapeutic penetrating keratoplasty;BSCVA = best spectacle corrected visual acuity; 1 Chi-square; 2Independent t-test.

(Table 2) shows the characteristics and the outcomes for Group 1 and Group 2. Follow-up period was similar for both groups, being 117.0 + 79.61 months in Group 1, and 105.50 + 60.90 months in Group 2 (p = 0.376). The mean clinical treatment time between the first symptoms and surgical procedure was 1.80 + 0.915 months in group 1, and 7.83 + 2.48 months in group 2 (p < 0.001).

Group 1

Group 2

P value

Time from symptoms to PK, months

1.80 ± 0.915

7.83 ± 2.48

< 0.001

Follow-up time, months

117 ± 79.61

105.50 ± 60.90

0.376

Post-treatment BSCVA (logMAR)

0.61 ± 1.07

0.98 ± 0.85

0.4162

Post-BSCVA Snellen ≥ 20/40  

9 (52.9%)

2 (33.3%)

0.4081

Surgical margins, clear

4/10 (40%)

2/4 (50%)

0.2771

Recurrence

2 (11.8%)

3 (50%)

0.0511

Rejection

6 (35.3%)

4 (66.7%)

0.1831

Glaucoma

3 (17.6%)

4 (66.7%)

0.0251

Table 2: Results of the 23 eyes undergoing therapeutic penetrating keratoplasty for Acanthamoeba keratitis; PK = therapeutic penetrating keratoplasty; BSCVA = best spectacle corrected visual acuity; 1 Chi-square; 2 Independent t-test.

Patients in Group 1 achieved a final mean BSCVA of logMar 0.61 + 1.07 versus 0.98 + 0.85 in Group 2, which corresponds to BSCVA Snellen 20/80 (logMar 0.60) and 20/200 (logMar 1), respectively (p = 0.416). Within Group 1, nine eyes (52.9%) achieved a final BSCVA equal to or better than Snellen's 20/40, while this percentage was 33.33% (2/6) in Group 2 (p = 0.408). Analyzing the improvements in the BSCVA, 94.1% (16/1) of the eyes had a final vision better than the baseline in Group 1 and 66.7% (4/6) in Group 2 (p = 0.86).

Recurrence of the AK infection occurred in 11.8% (2/17) of the early PK group (Figures 1 and 2), and in 50% (3/6) of the eyes that underwent a late therapeutic PK (more than five months from the symptoms) (Figure 3 and 4) (p = 0.051). Cornea rejection was the most reported complication following PK, and it affected 35.3% (6/17) of the eyes receiving early surgical treatment in Group 1 versus 66.7% (4/6) of the eyes in Group 2 (p = 0.183).

 

Figure 1: Acanthamoeba keratitis in a scleral contact lens wearer post-PK for keratoconus,with failure to clinical treatment for two months.

 

Figure 2: The same eye of Fig 1 shows the postoperative outcome one year after keratoplasty - no signs of recurrence.

 

Figure 3: Acanthamoeba keratitis was clinically treated for 15 months before surgery.