INTRODUCTION
Refractive surgery is an effective surgical procedure for correcting refractive errors, such as myopia, hyperopia, and astigmatism.1 The number of patients undergoing keratorefractive surgery has increased significantly in recent years as a result of rising prevalence of refractive errors and the rapid development of technology in this field.2,3 According to a nationwide population-based cross-sectional study, from 2008 to 2015, Korea's cumulative prevalence of refractive surgery increased by more than 10%.4 Although the development of keratorefractive surgery, including radial keratotomy (RK), astigmatic keratotomy (or arcuate keratotomy, AK), photorefractive keratectomy (PRK), laser-assisted subepithelial keratectomy (LASEK), laser-assisted in situ keratomileusis (LASIK), and small incision lenticule extraction (SMILE) with excimer lasers or femtosecond lasers, has increased the precision and safety for correcting refractive errors, infectious keratitis (IK), a rare (0.0004%) but potentially devastating complication after refractive surgery, should be paid sufficient clinical attention.5
In 1979, Dr. Fyodorov performed the first RK procedure, which was widely promoted worldwide after 1981, and the first case of bacterial keratitis after RK was reported in 1983.6 After that, PRK was introduced in 1988, and gram-positive organisms became the most common pathogens of infection because of the larger epithelial defect resulted from PRK.7 Laser-assisted in situ keratomileusis was developed in 1990 and gradually overtook other methods for correcting refractive errors while maintaining an intact corneal epithelium. Based on the flap-bed interface, a potential site for microbial infection, Mycobacterium was found to be the most frequent causative organism after LASIK.8,9 Although SMILE has excellent outcomes with good predictability, stability, and effectiveness, first performed by Sekundo and Blum in 2008,10 complications like diffuse lamellar keratitis or IK have also been reported recently.10–13
Although the qualitative description of IK after keratorefractive surgery was reviewed in 2016, quantitative and statistical analyses of some parameters were lacking, which were essential to make an early diagnosis and initiate treatment for clinicians.2 Considering different procedures that were popular in different eras and the characteristics of various surgeries, this study aimed to integrate existing data of IK after different keratorefractive surgeries to analyze the onset time, clinical manifestation, risk factors, microbiological profile, treatment, and outcomes.
MATERIALS AND METHODS
Search Strategy
To find pertinent studies, databases including PubMed, Ovid Embase, Web of Science, and CLNAHL were searched from January 1979 to March 2022. The following search terms were used, either individually or in various combinations: infectious keratitis, refractive surgery, astigmatic keratotomy, arcuate keratotomy, laser in situ keratomileusis, photorefractive keratectomy, radial keratectomy, laser-assisted subepithelial keratomileusis, small incision lenticule extraction, and intracorneal ring segments. In addition, we restricted “English” as the language of literature and the document type to “case reports or case series” because these document types offer specific descriptions about the infection.
Inclusion and Exclusion Criteria
The selected literature must be able to identify infectious keratitis through clinical presentation, scrapings, culture, molecular diagnostics, or in vivo confocal microscopy, among other methods. Articles reporting previously published cases or lacking the necessary details fell under the exclusion criteria. Cases with no ancillary or laboratory tests conducted were also disqualified. Furthermore, herpes simplex virus (HSV) infections were disregarded because the HSV infections are reactivations of dormant viruses rather than new infections.
Data Extraction
According to the purpose of this study and inclusion criteria, the literature evaluation scale and the data extraction scale were evaluated by one researcher (Z.J.Z.). Two researchers (J.M.L. and Z.Y.W.) independently extracted data from studies. If there was any disagreement between these two investigators, a third researcher (Q.F.L.) checked the extracted data. Four aspects of each included article were taken into consideration: basic information from the literature, the type of surgery, the diagnosis of infectious keratitis, and the course of treatment. More specifically, the title of study, name of the first author, year of publication, number of cases, age, gender, and type of surgery were documented. The afflicted eyes, presenting symptoms, the interval between refractive surgery and the initial symptoms, risk factors, best-corrected visual acuity (BCVA) at the first visit, and the slit-lamp examination findings were also recorded. The causative organisms, treatment period, treatment methods, and final BCVA after treatment were noted.
Postrefractive surgery keratitis can be classified as early-onset keratitis (occurring within 7 days of refractive surgery) and late-onset keratitis (occurring more than 7 days after refractive surgery).9 To ensure consistency, one researcher extracted all the aforementioned data into Microsoft Excel.
Statistical Analysis
Data were analyzed using the R program (V.4.0; R Foundation for Statistical Computing, Vienna, Austria) with a Meta package. Summary statistics were calculated for all variables. The 1-way ANOVA test was used to detect the variation of these parameters among different refractive surgeries, and for nonnormal distribution parameters or uneven variance, the Kruskal–Wallis test was used. The value of P<0.05 was considered statistically significant.
RESULTS
Study Characteristics
From the selected databases, 946 potentially relevant references were identified. In total, 687 records were screened after duplication and 128 full-text articles were assessed for eligibility after title and abstract screening. Finally, 84 studies meeting the inclusion criteria were included in this review, and 306 infectious eyes (involving 279 patients) after refractive surgery were analyzed. The mean age of patients was 36.9±11.0 years (ranging from 16 to 69 years [one patient underwent LASIK at the age of 69 years14]). One hundred thirty-four cases (48.1%) were male, and 145 cases (51.9%) were female. There were 9 cases reported from RK, 8 cases from AK, 83 cases from PRK, 149 cases from LASIK, 24 cases from ICR implantation, 26 cases from LASEK, 2 cases from Epi-LASIK, and 6 cases from SMILE (see Supplementary Material 1, https://links.lww.com/ICL/A262).
Risk Factors or Potential Factors of Infection
Information about specific predisposing factors was available from 139 cases (49.8%) after keratorefractive surgery. Preoperatively, both ocular and systemic conditions, including ocular inflammation and diabetes, may raise the risk of infection. Thirteen of these patients had a history of blepharitis, meibomitis, and dry eyes.14–16 Diabetes mellitus was discovered in four cases (Table 1).55,56
TABLE 1. -
Risk Factors for Different Keratorefractive Surgeries
| Surgery |
Risk Factors |
Cases |
Reference |
| RK |
Meibomitis |
1 |
17
|
|
Eye rubbing |
1 |
18
|
|
Prolonged use of topical corticosteroids |
1 |
19
|
| PRK |
Manipulation of contact lens |
26 |
7,14,16,20–33
|
|
Dry eye |
9 |
15,16,25,29
|
|
Healthcare professional |
9 |
7,16,26
|
|
Blepharitis |
5 |
15,16
|
|
Ocular trauma |
3 |
16
|
|
Contamination of surgical procedure |
3 |
32
|
|
Diabetes mellitus |
2 |
16
|
|
Frequent hospital encounters |
2 |
31
|
|
Corneal transplantation |
1 |
16
|
|
Inhaled corticosteroids |
1 |
22
|
| LASIK |
Contamination of surgical equipment |
13 |
34–36
|
|
Healthcare professional |
10 |
15,26
|
|
Contamination of surgical procedure |
9 |
37,38
|
|
Contamination of operating room |
7 |
39–41
|
|
Enhancement procedure |
3 |
42,43
|
|
Prolonged use of topical corticosteroids |
2 |
44
|
|
Contact with pets |
2 |
45–47
|
|
Exposed to dust |
2 |
45,48
|
|
The same instruments were used for both eyes |
2 |
49,50
|
|
Manipulation of contact lens |
2 |
42,51
|
|
Delayed reepithelialization of the corneal surface |
2 |
45,52
|
|
Contact with cereal seeds |
1 |
53
|
|
Eye rubbing |
1 |
54
|
|
Punctal plugs |
1 |
45
|
|
No antibiotic used |
1 |
45
|
|
No betadine used |
1 |
45
|
|
Dry eye |
1 |
43
|
| LASEK |
Health care professional |
1 |
15
|
|
Facial nerve palsy |
1 |
15
|
|
Blepharitis |
1 |
15
|
| ICR implantation |
Ring position (horizontal) |
4 |
14
|
|
Diabetes mellitus |
2 |
55,56
|
|
History of using rigid contact lens |
1 |
57
|
|
Eye rubbing |
1 |
55
|
|
Manipulation of contact lens |
1 |
55
|
| Epi-LASIK |
Health care professional |
1 |
58
|
LASEK, laser-assisted subepithelial keratectomy; LASIK, laser-assisted in situ keratomileusis; PK, penetrating keratoplasty; PRK, photorefractive keratectomy.
There were 33 cases (23.7%) in total associated with contamination during refractive surgery. Improper sterilization of surgical tools was reported in a number of cases of infectious keratitis after LASIK.34 Holmes et al.59 reported seven patients of infectious keratitis after LASIK caused by Mycobacterium, which was also isolated from the source ice machine's drain. Garg et al. reported a case of bilateral infectious keratitis after LASIK that may be caused by using the same instruments for bilateral surgery. Karp45 also reported one case of IK caused by Staphylococcus aureus without using povidone iodine and two cases with no postoperative antibiotic eyedrop used because of allergy. Predisposing risk factors for IK after PRK included breakdown of the corneal epithelium and the use of a bandage contact lens, particularly in patients with poor contact lens hygiene.7,60 Risk factors were mentioned in 61 patients after PRK. Of the 61 patients, 26 (42.6%) had a history of postoperative bandage contact lenses. With a hazard ratio of 2.92, it was noted that the PRK procedure carried a higher risk of developing postoperative microbial keratitis than LASIK.61 According to Hofling-Lima et al.55 and Tabatabaei et al.,14 Ferrara ring implantation and the horizontal position of the ICR implantation segment were linked to a higher incidence of IK after ICR.
Postoperatively, epithelial defects, delayed epithelialization, overuse of corticosteroids, and a delay in antibiotics administration can all increase the risk of infection after surgery. Chung et al.52 reported that a delayed epithelialization of the corneal surface and a 2-week course of postoperative corticosteroids were to blame in a case of fungal keratitis after LASIK. And according to Karp et al.45 and Tuli et al.,46 two patients developed fungal keratitis after LASIK, which may have been directly brought on by a fungus that infected cat skin. Twenty-three individuals were infected with methicillin-resistant Staphylococcus aureus (MRSA), all of whom worked in healthcare settings or visited hospitals frequently.
Clinical Manifestations
Of the 306 eyes, the mean onset time of IK after refractive surgeries was 22.9±38.7 days (range: 1 day to 3 years). There were 161 cases in the early-onset group (within 7 days) and 145 cases in the late-onset group (>7 days). Depending on the refractive surgery, the onset time of IK was 2.2±1.0 days (range: 1–4 days) after SMILE, 6.9±6.1 days (range: 2–34 days) after LASEK, 11.0±24.0 days (range: 1–160 days) after PRK, 40.8±60.2 days (range: 3–180 days) after ICR implantation, and 27.3±41.9 days (range: 1–210 days) after LASIK. There was a statistical difference in the onset time of infection after different refractive surgeries (P<0.001).
Clinical symptoms were reported in 169 eyes (148 cases) with IK after refractive surgery. The most common symptoms were eye pain (62.8%), decreased or blurry vision (56.1%), photophobia (46.6%), eye redness (45.3%), and irritation (29.7%). Furthermore, 167 eyes (98.8%) showed corneal infiltration compared with 47 eyes (27.8%) with epithelial defects, 20 eyes (11.8%) with anterior chamber reactions, and 32 eyes (18.9%) with hypopyon.
Microbiological Profile
Among 306 eyes, 257 (84.0%) were culture positive. Staphylococcus aureus (68, 26.5%) was the most frequent isolate from IK after refractive surgery, followed by Mycobacterium (62, 24.1%), coagulase-negative Staphylococcus (CNS) (23, 8.9%), and Aspergillus (14, 5.4%) There were 10 eyes (4.1%) with polymicrobial infections (see Supplementary Material 2, https://links.lww.com/ICL/A263).
In the early-onset group, S. aureus was the most common isolate, which accounted for 63 (39.1%) of the 161 infectious eyes, followed by Aspergillus (10, 6.2%), CNS (10, 6.2%), Streptococcus pneumoniae (8, 5.0%), and Mycobacterium (7, 4.3%). In the late-onset group (145 eyes), the most prevalent bacteria were Mycobacterium (from 55 eyes, 37.9%), followed by CNS (from 12 eyes, 8.3%) and Nocardia (from 5 eyes, 3.4%).
In this study, IK after PRK was reported in 90 eyes, of which the most common isolated pathogens were S. aureus (35, 38.8%), CNS (8, 8.9%), and S. pneumoniae (7, 7.8%). Among 149 eyes with IK after LASIK, the most prevalent microorganisms were Mycobacterium (62, 44.0%), followed by S. aureus (21, 14.9%) and Aspergillus (11, 7.8%). CNS (11, 47.8%) and S. aureus (6, 26.1%) were the most frequent isolates in IK after ICR implantation (Table 2). It was noteworthy that four eyes developed Acanthamoeba keratitis after RK, PRK, and LASIK.
TABLE 2. -
Clinical Features,
Treatment, and Prognosis of
Infectious Keratitis After Refractive Surgeries
| Type |
Isolated Organism (No.) |
Onset Time (Days) |
Initial BCVA |
Medication |
Surgery |
Final BCVA |
| RK |
Diphtheroids (2) |
11 |
NA |
Vancomycin/ciprofloxacin/prednisolone |
None |
<20/20 (1), <20/40 (1) |
|
CNS (1) |
1 |
NA |
Cefazolin/tobramycin |
None |
≥20/20 |
|
Aspergillus (1) |
17 |
NA |
Amphotericin/itraconazole |
PK |
<20/20 |
|
Acanthamoeba (1) |
42 |
CF/2 ft |
Neomycin/propamidine/PHMB |
None |
NA |
| AK |
Staphylococcus aureus (1) |
21 |
CF |
Vancomycin/tobramycin/dorzolamidetimolol |
None |
20/30 |
|
CNS (1) |
18 |
20/60 |
Vancomycin/amikacin |
None |
20/20 |
|
Microsporidiosis(1) |
60 |
20/30 |
Oral albendazole/fumagillin |
None |
20/70 |
|
Pseudomonas (1) |
3 years |
Light perception |
Amikacin/oral ciprofloxacin |
None |
20/50 |
| PRK |
S. aureus (35) |
3±2.1 |
<20/40 (4), <20/200 (5), NA (26) |
Ofloxacin/ciprofloxacin/vancomycin/cefazolin |
PK (3) |
≥20/20 (14), <20/20 (8), <20/40 (3), <20/200 (1), NA (9) |
|
CNS (8) |
2±0.8 |
NA |
Ofloxacin/ciprofloxacin/vancomycin/cefazolin |
None |
≥20/20 (3), NA (5) |
|
Streptococcus pneumoniae (7) |
3±1 |
<20/200 (1),
NA (6) |
Ofloxacin/ciprofloxacin/vancomycin/cefazolin |
None |
<20/20 (2), <20/40 (2), NA (3) |
| LASIK |
Mycobacterium (62) |
33±38 |
≥20/20 (5), <20/20 (10), <20/40 (11), <20/200 (14), NA (22) |
Arbekacin/clarithromycin |
LK (2), PK (6), flap excision (16) |
≥20/20 (17), <20/20 (18), <20/40 (18), <20/200 (4), NA (5) |
|
S. aureus (21) |
4±3 |
≥20/20 (1), <20/20 (2), <20/40 (2), <20/200 (1), NA (15) |
Vancomycin/cefazolin/gentamicin/ciprofloxacin |
Flap excision (1) |
≥20/20 (5), <20/20 (10), <20/40 (6) |
|
Aspergillus (11) |
6±3.3 |
<20/40 (2), <20/200 (9) |
Voriconazole/natamycin |
PK (6), flap excision (4) |
≥20/20 (2), <20/20 (4), <20/40 (4), <20/200 (1) |
| LASEK |
S. aureus (3) |
5±1.6 |
NA |
Vancomycin/moxifloxacin |
None |
≥20/20 (1), <20/20 (1), <20/40 (1) |
|
CNS (2) |
4 |
NA |
Moxifloxacin/ofloxacin |
None |
≥20/20 (1), <20/40 (1) |
|
Pseudomonas (1) |
10 |
NA |
Tobramycin, amikacin |
None |
<20/20 |
|
Epidermophyton floccosum (1) |
10 |
NA |
Natamycin |
None |
<20/20 |
|
Candida (1) |
5 |
NA |
Voriconazole/ciprofloxacin |
None |
<20/20 |
| ICRS |
CNS (11) |
33±38.9 |
<20/20 (1), <20/40 (5), <20/200 (1), NA (4) |
Vancomycin/cefazoline |
Ring removal |
≥20/20 (2), <20/20 (3), <20/40 (4), <20/200 (1), NA (1) |
|
S. aureus (6) |
39±70.3 |
<20/20 (4), NA (2) |
Amikacin/cefazolin |
PK (2), ring removal |
≥20/20 (3), <20/20 (1) |
|
S. vestibularis (1) |
21 |
<20/200 |
Erythromycin |
Ring removal |
<20/200 |
|
Nocardia (1) |
NA |
NA |
NA |
None |
NA |
|
Pseudomonas (1) |
NA |
NA |
NA |
PK (1) |
NA |
| Epi-LASIK |
S. aureus (2) |
3±1 |
<20/200 (2) |
Vancomycin |
PK (1) |
>20/20 (1), <20/20 (1) |
| SMILE |
S. pneumoniae (2) |
2 |
<20/200 (2) |
Rifamycin/ofloxacin/dexamethasone |
No |
<20/20 (2) |
|
Aspergillus (2) |
3±1.5 |
<20/20 (1), <20/200 (1) |
Voriconazole/levofloxacin/oral itraconazole |
PK (1) |
<20/40 (1), NA (1) |
|
S. aureus (1) |
2 |
NA |
Vancomycin |
None |
≥20/20 |
BCVA, best-corrected visual acuity; CF, counting fingers; CNS, coagulase-negative Staphylococcus; ft, feet; LASIK, laser-assisted in situ keratomileusis; LK, lamellar keratoplasty; NA, not applicable; PHMB, polyhexamethylene biguanide; PK, penetrating keratoplasty; PRK, photorefractive keratectomy; SMILE, small incision lenticule extraction.
Treatment and Prognosis
In this study, 270 cases of IK after refractive surgeries with detailed treatment regimens were reviewed, of which 150 (55.5%) could be successfully cured by medical therapy alone and 45 required keratoplasty (16.7%). Medical treatment depended on microbial culture results. The final BCVA after medical therapy was as follows: 20/20 or better in 55 cases (37.0%), 20/40 or better in 115 cases (76.5%), and worse than 20/40 in 35 cases (23.5%).
Among the 61 cases of Mycobacterium infection, 9 (14.8%) were treated with topical amikacin alone, 14 (23.0%) with clarithromycin eyedrops, and one (1.6%) with topical moxifloxacin as single-agent therapy. A topical combination of amikacin, clarithromycin, and fourth-generation fluoroquinolones was reported in 37 cases (60.7%). Clarithromycin was systematically administrated to 20 patients (32.8%) based on the treatment mentioned above. The course of treatment after Mycobacterium infection lasted anywhere between 4 weeks and 12 months. Infections caused by Staphylococcus sp. were often treated by topical broad-spectrum antibiotics such as third- or fourth-generation fluoroquinolones, vancomycin, or cephalosporins. Only 7 (10.9%) of the 64 cases with available information received monotherapy, most (48, 75.0%) were treated with duplex-agent or triple-agent therapy, and 9 cases (14.1%) were treated with combinations of four or more drugs. Of the 14 Aspergillus infectious cases, only 2 (14.3%) were treated with one antifungal eyedrop, one of which was amphotericin B and the other was natamycin. Twelve patients (85.7%) received two or three antifungal eyedrops containing natamycin, amphotericin B, or voriconazole; meanwhile, 9 patients (64.3%) received oral conazole.
One hundred twenty eyes (44.5%) underwent surgical procedures such as keratoplasty, ring removal, flap lift, and flap amputation. In cases where the eye was nearing perforation, had a full-thickness infiltration, or was medically unresponsive, therapeutic keratoplasty may be considered. In our review, therapeutic keratoplasty was performed in 45 infectious cases (16.7%), including 42 for penetrating keratoplasty and 3 for deep anterior lamellar keratoplasty. The final BCVA after keratoplasty was as follows: 20/20 or better in 8 cases (17.8%), 20/40 or better in 20 cases (44.4%), and worse than 20/40 in 25 cases (55.5%). In addition, 2 patients (0.7%) underwent phototherapeutic keratectomy here. Two patients (0.7%) experienced endophthalmitis, and one patient (0.4%) required enucleation.
Of the 83 patients who had post-PRK keratitis, 75 (90.4%) responded well to medication, and only 8 (9.6%) needed penetrating keratoplasty; the final BCVA after treatment was 20/20 or better in 30 cases (36.1%), 20/40 to 20/20 in 12 cases (14.5%), and worse than 20/40 in 42 cases (50.6%). In post-LASIK infections, flap lift was essential to culture the infiltrate secretion and irrigate the interface with antibiotics, such as moxifloxacin for early-onset keratitis and amikacin for late-onset keratitis. When the flap was melting, densely infiltrated, or failed to improve clinically after antibiotic treatment, early flap amputation was advised.62,63 In this study, flap lift was performed in 92 of 149 eyes (61.7%), and flap amputation was necessary in 27 eyes (18.1%). Furthermore, 32 eyes (21.5%) required keratoplasty, including 3 for lamellar keratoplasty and 29 for penetrating keratoplasty, and the BCVA after treatment was 20/20 or better in 42 cases (28.2%), 20/40 to 20/20 in 40 cases (26.8%), and worse than 20/40 in 67 cases (45.0%) (Fig. 1). In 14 of 24 eyes (58.3%) with IK after ICR implantation, the rings were removed and the pockets were irrigated with fortified antibiotics like vancomycin 1 mg/0.1 mL. The recommended treatments for moderate keratitis after SMILE included interface wash and collagen cross-linking with photoactivated riboflavin (PACK-CXL) in addition to fortified eyedrops. Interface rinsing occurred in 5 eyes (83.3%) and PACK-CXL in 2 cases (33.3%) that underwent SIMLE in our study. After ICR implantation and SMILE infection, penetrating keratoplasty was necessary in 16.7% of infectious cases. Furthermore, there was no statistically significant difference in the rate of corneal transplantation among various refractive postoperative infections (P=0.150).
;)
FIG. 1.: Best-corrected visual acuity before and after treatment of infectious keratitis after refractive surgeries.
DISCUSSION
The popularity of keratorefractive procedures has grown in recent years. Despite being a rare complication with incidence rates of 0.017% to 0.3% after PRK, 0.0001% after LASEK, and 0.005% to 0.035% after LASIK, infectious keratitis can result in remarkable visual loss.5,61,64,65 In this review, 84 studies involving 306 cases were integrated to investigate related risk factors, clinical manifestation, microbiological profile, treatment, and prognosis.
It was critical to document the patient's systemic illnesses and thoroughly examine the ocular surface. Patients with blepharitis or severe meibomian gland disease should be instructed to control these conditions days or weeks before surgery. Cleaning the eyelids within 3 days preoperatively was suggested to reduce the bacterial load on the corneal surface, which was believed to be associated with a lower risk of infection.15 In addition, Soleimani et al.66 found that the increased perioperative use of face masks during the COVID-19 pandemic increased the rate of IK after PRK. This might be explained by the fact that masks divert airflow containing oral flora to the eyes, raising the risk of infection in an already compromised cornea.67
Intraoperative contaminations were the most frequent causes of post-LASIK infection, and possible sources of contamination included contaminated operating rooms, inadequately sterilized surgical instruments, and usage of the same set of surgical instruments for both eyes. Surgeons should pay more attention to these to reduce the risk of infection. Because of the significant epithelial defect caused by surface ablation procedures, which gives infectious microbes a place to adhere and multiply, PRK has been associated with a higher risk of microbial keratitis than LASIK. Afsharpaiman et al.,5 however, explained that the manipulation of more corneal tissue to create a flap and the need for more tools during LASIK may increase the risk of infection. Currently, mechanical microkeratomes and femtosecond laser microkeratomes are the two techniques used to create LASIK flaps. When compared with mechanical microkeratome, femtosecond laser creates flaps with greater precision in thickness and fewer complications like epithelial ingrowth.68 However, Schallhorn et al.61 found no correlation between flap type (mechanical microkeratome vs. femtosecond laser) and risk of microbial keratitis. For IK after ICR implantation, the triangular shape and depth of the Ferrara ring segments can lead to superficial placement, and Ferrara implants require multiple incisions.14 Additionally, the ICR implantation segment's horizontal position may make it easier for bacteria to move from the eyelid margins into the tunnel in horizontal incisions.55
The onset time of IK varied greatly among different surgeries. Clinicians need to make an appropriate follow-up schedule depending on the type of refractive surgery. The onset of IK after SMILE was the quickest; in this study, the infectious manifestations appeared within 7 days. Most cases of IK after PRK occurred within a week, which was consistent with the results from other authors.69 In contrast, 63.8% of IK after LASIK were classified as late-onset IK (approximately 1 month), probably because mycobacterial infections were more likely to present 10 or more days after surgery than other organisms.9,63 Although it is unusual to have IK after refractive surgeries in several years, Esin et al. reported keratitis 3 years after AK over the keratotomy incision in a 56-year-old woman.70 Mandelbaum et al.71 hypothesized that an abnormal epithelial architecture in the region of the incision months to years after radial keratotomy, coupled with redistribution of the tear film because of changes in corneal topography, may predispose to late corneal infection.
Gram-positive cocci were the most frequently isolated pathogens in infectious keratitis after PRK, ICR, SMILE, and early LASIK, whereas Mycobacterium became the most common pathogen after late LASIK.7,14,63,72 Atypical Mycobacterium infection could be prevented or reduced by raising awareness, enhancing sterile procedures, or using fourth-generation fluoroquinolones timely.62,64
In cases suspected of IK after refractive surgery, topical broad-spectrum antibiotics should be administered initially based on clinical presentation. For clinically suspected bacterial keratitis, a fourth-generation topical fluoroquinolone, such as moxifloxacin, alternating with cefazolin at 50 mg/mL every 30 minutes was recommended.65 However, if the patient was a healthcare worker who was more likely to carry MRSA, vancomycin was recommended as a substitute for cephazolin. Fungal keratitis often presents with dense infiltrate, feathery borders, satellite lesions, and hypopyon, and one or more topical antifungals are usually used in conjunction with systemic administration of oral antifungals.73 Cases of Acanthamoeba keratitis should be treated with 0.02% polyhexamethylene biguanide (PHMB) with 0.02% chlorhexidine eye drops or voriconazole.74 Because of overlapping clinical features among different types of IK, microbiological testing was important. Wroblewski et al.28 recommended that any infiltrate larger than 2 mm, associated with anterior chamber reaction or considerable pain, or that does not improve with empirical therapy should be smeared and cultured. The suggested treatments for post-LASIK infectious keratitis included an immediate flap lift and irrigation, culture, and irrigation of the flap interface with broad-spectrum topical antibiotics, which may be related to a better visual outcome.9,48,75 In cases with flap necrosis or poor clinical improvement, flap excision may be required to reduce the microbes and improve antibiotic penetration. For IK after ICR implantation, it is necessary to remove the rings and irrigate the tunnel or pocket with antibiotics.14,76 When the response to these treatments was still poor, as in the case of full-thickness or extensive infiltration, or perforation that was almost complete, therapeutic keratoplasty should be performed. In comparison with LASIK's flap, infectious keratitis after SMILE may be more difficult to treat because the infection may spread quickly within the closed interface, which is more difficult to access. It is important to open the interface for corneal scrapings in these situations because opening the interface aid in the targeted treatment of the infectious agent. However, Tommy et al. asserted that irrigation of the corneal cap-stromal bed interface might be challenging and affect postoperative visual outcomes. Tommy et al. used PACK-CXL to treat a case of bacterial keratitis successfully. The prevalence of corneal transplantation was 16.7%, and the final BCVA after treatment was worse than 20/40 in 55.5% of cases, which had serious repercussions, including moderate or severe reductions in visual acuity. Infectious keratitis after keratorefractive surgeries should be a greater concern for clinicians to prevent negative outcomes.
Our study integrates and synthesizes data from case series reports about IK after keratorefractive surgery, which is valuable to help clinicians understand the features and guide the management of infectious keratitis. However, there are some potential limitations. First, there were discrepancies in the quality of the articles enrolled. In some articles, the patient's medical history, clinical diagnosis, and treatment information may have been lacking. Second, the small sample sizes of some surgeries would compromise the validity of the study's findings.
In summary, our study provides comprehensive analysis of the clinical features of infections after different keratorefractive surgeries, which will be helpful for clinicians to better understand IK after various refractive surgeries and subsequently lessen its occurrence. Most of the infections after keratorefractive surgery happen within a week, whereas more than half of cases after LASIK happen after about a month. Gram-positive cocci are the most frequently isolated pathogens in IK after PRK, ICR segments, SMILE, and early LASIK, whereas Mycobacterium is the most prevalent pathogen in late LASIK. Early-onset keratitis should be treated with broad-spectrum antibiotics, as should immediately flap lift and culture, irrigation for moderate-to-severe infection after LASIK, ring removal with antibiotic-treated tunnel or pocket irrigation for ICR implantation, and interface wash for SMILE. If the aforementioned treatments are ineffective, corneal transplantation should be taken into consideration. Early recognition and timely and appropriate treatment can prevent visual loss in this rare complication after keratorefractive surgery.
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