Clinical Outcomes of Infectious Keratitis Associated with Contact Lens Wear Following Penetrating Keratoplasty: A Case Series

doi:10.21203/rs.3.rs-3637604/v1

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Clinical Outcomes of Infectious Keratitis Associated with Contact Lens Wear Following Penetrating Keratoplasty: A Case Series

https://doi.org/10.21203/rs.3.rs-3637604/v1

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Objectives

To report on the clinical characteristics, and outcomes of patients who developed infectious keratitis associated with contact lens wear following penetrating keratoplasty (PK).

Methods

A retrospective chart review was performed to identify all patients who underwent PK between November 2012 and January 2023 at a single tertiary referral practice, and subsequently developed contact-lens related infectious keratitis. Electronic medical records of 74 identified patients were reviewed to obtain data about demographics, ocular history, contact lens usage, microbial culture reports, visual acuity, treatment, and clinical outcomes.

Results

Contact-lens-associated infectious keratitis occurred in 9 patients, more frequently in males (66%), and patients had a mean age of 54.5 +/- 11.8 years old. The identified causative organisms included: Moraxella nonliquefaciens (N = 1), Pseudomonas aeruginosa (N = 1), Stenotrophomonas maltophilia (N = 3), Staphylococcus epidermidis (N = 1), Streptococcus mitis (N = 1), Candida albicans (N = 1), Candida parapsilosis (N = 2), and Acanthamoeba (N = 1). Contact lenses were used following PK for an average of 9.1 +/- 10.8 months before development of keratitis. Patients were followed for 31.8 +/- 30.2 months after infection. The mean best corrected visual acuity without contact lenses prior to infection was 20/150 and decreased to 20/260 post-infection. Complications following the contact-lens-associated infectious keratitis included: central corneal haze (N = 8), chronic corneal epithelial defects (N = 3), perforation (N = 3), endophthalmitis (N = 1), and enucleation (N = 1). Three grafts required repeat PK.

Conclusions

Contact-lens-associated infectious keratitis following PK have high rates of complication. Patients should be monitored closely for signs of infection.

Health sciences/Diseases/Eye diseases/Corneal diseases

Health sciences/Signs and symptoms/Eye manifestations

Penetrating keratoplasty

infectious keratitis

contact lens

Contact lenses are used for vision correction and rehabilitation after many ophthalmic procedures including penetrating keratoplasty (PK). PK is associated with several post-operative complications, including neurotrophic keratopathy, persistent corneal epithelial defects, corneal ulcers, graft rejection, irregular astigmatism, and infectious keratitis.¹ These complications can lead to delayed or suboptimal visual rehabilitation. The use of contact lenses following PK have thus become an integral part of post-operative visual rehabilitation.² There are several contact lens types and designs used for the management of post-keratoplasty corneas. Gas permeable and scleral lenses are utilized to correct irregular astigmatism,^3,4 while soft lenses are used to treat regular refractive error and corneal epithelial defects.⁵ Several factors influence the selection and fitting of contact lenses, including visual requirements, corneal surface condition, and the refractive status of the eye.⁵

Although safe and easy to use, contact lenses in normal corneas may increase risk of developing infectious keratitis.⁶ The annual incidence of contact-lens-associated keratitis is between 2–4/10,000.⁶ Keratitis is most commonly caused by bacteria in 90% of cases and less commonly due to Acanthamoeba and fungi.^6–8 These infections are often limited if diagnosed and treated early, but may require intensive antibiotic treatment or emergency corneal transplantation if they present late with melting, wound dehiscence, or perforation.⁹ To our knowledge, the outcome of contact-lens-associated infectious keratitis following PK have not been reported. In this study, we report the clinical outcomes of patients who developed infectious keratitis associated with contact lens wear following PK.

A retrospective review of medical records of patients using contact lenses following PK was conducted at the University of Minnesota, Department of Ophthalmology and Visual Neurosciences. This study was approved by the Institutional Review Board of the University of Minnesota complying with the principles outlined in the Declaration of Helsinki. Patients receiving medical treatment at the University of Minnesota were identified using ICD codes for penetrating keratoplasty and corneal transplant status. Current procedural terminology (CPT) codes were also used to identify patients who received a PK (aphakia), PK (phakia), and PK (pseudophakia). Of the patients that were identified using these codes, the patients that received a prescription for long-term contact lenses following PK were further identified.

Inclusion and Exclusion Criteria

Patients of all ages that received a PK between November 2012 and January 2023 and later developed contact-lens-associated infectious keratitis were included in the study. All types of infectious keratitis (viral, fungal, acanthamoeba, and bacterial) were included. Cases of sterile ulceration or neurotrophic keratitis were excluded. Patients that had a prescription for contact lenses for longer than two weeks following PK were included in the study while those who were given contact lenses to treat a corneal surface disease in the immediate postoperative period for less than 2 weeks were excluded.

Population

After patients who were using contact lenses following penetrating keratoplasty were identified, the electronic medical records were reviewed. Data on patients' demographics, ocular history, contact lens usage, culture reports, visual acuity, treatment, and clinical outcomes were documented.

Statistical Methods

Continuous variables (age, gender, ocular history characteristics, contact lens usage variables, treatment duration, and visual acuity) were analyzed using the mean and standard deviation. Categorical variables (pathology, culture, and treatment) were presented as percentages. Outcome measures were calculated using Excel 2016 (Microsoft, Redmond, WA). To determine the mean acuity values, individual visual acuities were converted to Logmar values. The mean Logmar was calculated, then the equivalent Snellen value was reported.

In total, 74 patients were identified as having long-term contact lens use after PK during the study period. A total of 9 patients (12.2%) in this population developed contact-lens-associated infectious keratitis. The average age at the time of the PK was 54.5 +/- 11.8 years, with 66% of the patients being male (Table 1). These patients received a PK as treatment for a myriad of corneal pathologies including keratoconus (N = 1), corneal graft failure (N = 1), corneal melt (N = 2), corneal scar (N = 4), and corneal ulcer (N = 2), where one patient had both a corneal melt and corneal scar. The ocular history of patients included the following ocular comorbidities: dry eyes (N = 5, 55.6%), glaucoma (N = 3, 33.3%), previous penetrating keratoplasty (N = 4, 44.4%), limbal stem cell deficiency (N = 4, 44.4%), and ocular cicatricial pemphigoid (N = 1, 11.1%) (Table 1).

Table 1

Demographic Data of Patients with Contact-Lens-Related Infectious Keratitis.
Demographic Data
Age at transplant (years), mean +/- SD	54.4 +/- 11.8
Male, N (%)	6 (66.7%)
Female, N (%)	3 (33.3%)
Ocular History
Dry eyes, N (%)	5 (55.6%)
Previous penetrating keratoplasty, N (%)	4 (44.4%)
Glaucoma, N (%)	3 (33.3%)
Limbal stem cell deficiency, N (%)	4 (44.4%)
Ocular cicatricial pemphigoid, N (%)	1 (11.1%)
Contact Lens Usage
Time surgery to CL used (months), mean +/- SD	21.7 +/- 51.9
Total time of daily CL usage (hours) (4 patients), mean +/- SD	13.5 +/- 6.5
CL usage per week (days), N	7
CL usage until infection (months), mean +/- SD	9.1 +/- 10.8
Follow up duration after infection (months), mean +/- SD	31.8 +/- 30.2
Presence of corneal sutures, N (%)	6 (66.7%)
CL used for treatment of corneal epithelial defects, N (%)	3 (33.3%)
CL used for vision rehabilitation, N (%)	8 (88.9%)
CL = Contact Lens; N = Number; SD = Standard Deviation

The patients in this study used contact lenses for visual rehabilitation and corneal epithelial defects after PK. Of the nine patients, eight (88.9%) used contact lenses for vision rehabilitation and three (33.3%) used contact lenses for the treatment of corneal epithelial defects, with two patients (22.2%) using contact lenses for both indications at different points in time (Table 1). The average best corrected visual acuity without contact lenses prior to infection was 20/150 and decreased to 20/260 post-infection (Table 2). Seven patients were fitted with scleral lenses, one patient was fitted with soft lenses, and one patient was fitted with hybrid lenses. The average size of the scleral lenses was 16.6 +/- 1.3 mm, and the sizes of the soft and hybrid lenses were 14.5 mm and 17 mm respectively. The mean time after PK before patients began using contact lenses was 21.7 +/- 51.9 months. Patients wore contact lenses for an average of 9.1 +/- 10.8 months until an infection was diagnosed, and they used the lenses for an average of 13.5 +/- 6.5 hours per day (Table 1).

Table 2

Clinical Outcomes of Patients with Contact-Lens-Related Infectious Keratitis.
Clinical Outcomes
Patient	Culture	Non-Steroid Eye Drops Prior to Infection	Eye Drop Treatment	Oral Treatments	Duration of Treatment (months)	Complications	Surgical Treatment After Infection	Graft Clarity	BCVA with CL Prior to Infection	BCVA following Resolution
1	Moraxella nonliquefaciens	Artificial tears, Muro	Vancomycin, Tobramycin	-	1	Epithelial defect	No	Central scar	20/200	20/600
2	Pseudomonas aeruginosa	Timolol	Vancomycin, Tobramycin	-	2	Epithelial defect	No	Peripheral scar	20/40	20/30
3	Streptococcus mitis	Artificial tears, Restasis, Ofloxacin	Vancomycin, Tobramycin	-	1	Corneal perforation	Therapeutic PK, followed by enucleation	Graft replaced	20/250	NLP
4	Acanthamoeba	Artificial tears, Predhealon, Restasis, Serum tears	Polyhexamethylene Biguanide	Miltefosine	1	Corneal perforation	Therapeutic PK	Graft replaced	20/300	HM
5	Stenotrophomonas maltophilia, Candida parapsilosis	Artificial tears	Vancomycin, Tobramycin, Voriconazole	-	3	None	No	Peripheral scar	20/30	20/70
6	Stenotrophomonas maltophilia, Candida parapsilosis	Predhealon	Vancomycin, Tobramycin, Amphotericin, Fluconazole, Intravitreal vancomycin/ ceftazidime/ voriconazole	-	2.5	Corneal neovascularization, Endophthalmitis	Repeat PK four months after infection	Central scar	20/50	20/60
7	Stenotrophomonas maltophilia, Staphylococcus epidermidis, Candida albicans	Durezol, Timolol, Serum tears, Gentamicin	Vancomycin, Tobramycin, Amphotericin	-	1	Corneal perforation	Therapeutic PK	Graft replaced	20/125	N/A
8	Negative	Alphagan	Ofloxacin, Intravitreal vancomycin/ ceftazidime	Famciclovir	1	None	No	Clear graft	20/50	20/100
9	Not performed	Neo-poly-dex	Neo-poly-dex	-	2	Epithelial defect	No	Central scar	20/30	20/70
BCVA = Best Corrected Visual Acuity, CL = Contact Lens, HM = Hand Motion, NLP = No Light Perception, N/A = Not Available, PK = Penetrating Keratoplasty, VA = Visual Acuity

Of the eight patients that had cultures collected, three patients had keratitis that was caused only by bacterial agents, one patient had a parasitic infection, and three patients had an infection that was caused by both bacterial and fungal agents. One patient did not have any cultures collected (Patient 9), and one patient with a pre-operative history of Herpes Simplex Virus (HSV) had negative cultures and was presumed to have keratitis secondary to recurrent HSV (Patient 8) (Table 2). The causative organisms among infectious keratitis patients included: Moraxella nonliquefaciens (N = 1, 11.1%), Pseudomonas aeruginosa (N = 1, 11.1%), Stenotrophomonas maltophilia (N = 3, 33.3%), Staphylococcus epidermidis (N = 1, 11.1%), Streptococcus mitis (N = 1, 11.1%), Candida albicans (N = 1, 11.1%), Candida parapsilosis (N = 2, 22.2%), and Acanthamoeba (N = 1, 11.1%) (Table 2). Patients 5, 6, and 7 had polymicrobial keratitis. (Table 2).

Treatment of the infectious keratitis was dependent on the causative agent and the severity of the infection (Table 2). Slit lamp photos of Patient 1 and patient 7 resolution over time are presented in Fig. 1. The average duration of treatment for the nine patients was 1.6 +/- 0.7 months (Table 2). In addition, 44.4% of patients required an additional PK after the infection, and 33.3% of patients had corneal perforation (Table 2). Despite developing infectious keratitis, seven out of nine patients (77.8%) returned to use contact lenses after resolution of the infection (Table 1).

Corneal transplants, including PK, are relatively safe procedures but still carry a small risk of serious complications such as infection, glaucoma, rejection of the donor cornea, refractive error from irregular astigmatism, and retinal detachment.¹ Multiple factors, including contact lens wear, may have contributed to the development of infectious keratitis in post-PK patients. Song et al. reported that post-keratoplasty infectious keratitis affects patients of all age groups, with most cases reported for patients between 17–95 years of age.¹⁰ All nine patients who developed contact-lens related keratitis following PK in our series were within this age range. Risk factors for keratitis following keratoplasty include a procedural history of prior penetrating or endothelial keratoplasty and ocular surface disorders.¹¹ Post-operative neurotrophic keratitis, dry eyes, and chronic topical medications used to treat glaucoma can disrupt the ocular surface and lead to surface disease.^12,13 Many patients identified in this case series had previous PK, glaucoma, and dry eyes, which may have increased their risk of infectious keratitis. In addition, all patients were treated with steroid drops up until they developed infectious keratitis. Although steroid drops are required in treatment to reduce the risk of graft infection, it has been reported that the use of steroid drops may be a significant risk factor for post-keratoplasty infectious keratitis, especially in cases of fungal and Acanthamoeba infection.^10,14

The type of lens and duration of contact lens wear can affect the risk of developing contact-lens-associated infectious keratitis.^6,15 The incidence of microbial keratitis has been more widely reported for soft lenses than for rigid gas permeable lenses. Cheng et al. estimated that the incidence of microbial keratitis in normal corneas was 3.5/10,000 for daily-wear soft lens wearers, 20/10,000 for extended-wear soft lens wearers, and 1.1/10,000 for daily-wear rigid lens wearers.¹⁶ Scleral lenses may also be associated with a high risk of infectious keratitis compared to other types of contact lenses with reports between 0.5–1.6%.^17–20 Kawulok et al. reported on three patients that developed microbial keratitis associated with scleral lens wear and penetrating keratoplasty.¹⁷ Of the nine patients in our case series, seven patients wore scleral contact lenses, which suggests that this type of lens may be associated with risks of developing contact-lens-associated infectious keratitis, but comparative studies are needed to prove that theory. In addition, the prevalence of microbial keratitis after penetrating keratoplasty without the use of contact lens has been reported as between 1.8% and 12.1%.²¹ This makes it difficult to determine any direct causation or correlation between postoperative contact lens wear following PK and the development of infectious keratitis.

It is known that the duration of wear of contact lenses may increase the risk of developing an infection. The use of overnight soft contact lenses, compared to other types of contact lenses, causes the highest occurrence of infectious keratitis with a prevalence of 9.2–20.9/10,000 wearers, followed by a prevalence of 2.2–4.5/10,000 wearers for daily soft contact lenses.¹⁵ Patients in this series wore contact lenses seven days a week with mean duration of more than 12 hours a day. The length of time that patients wore contact lenses may have increased their risk of developing contact-lens-associated infectious keratitis.

Bacteria, most commonly Staphylococcus and Pseudomonas,²² is causative in 90% of contact-lens-associated infectious keratitis cases in normal corneas, with fungi and Acanthamoeba serving as less common causes.^6–8 Similarly, gram-positive bacteria, most commonly Staphylococcus species, have been cited as the most common causative agent of microbial keratitis following PK.^10,21 Ozlap et al. found that 55.5% of cases of microbial keratitis after PK were of bacterial origin, followed by 41.7% viral and 2.8% fungal.²¹ This case series identified a higher rate of fungal keratitis (33.3%) than reported in the literature. Steroid eye drops may have caused a local immunosuppression increasing the risk of fungal keratitis, although the small sample size might have contributed to this discrepancy.

Post-PK infectious keratitis without associated contact lens wear has been associated with many severe complications. Corneal perforation is seen in 4.9–35% of patients following post-keratoplasty infectious keratitis.¹⁰ In our study, three patients (33.3%) had corneal perforation. It has been reported that 39% of patients have persistent epithelial defects following resolution of post-keratoplasty infectious keratitis.¹⁰ Three patients (33.3%) developed persistent corneal epithelial defects in this case study. Another complication following PK infectious keratitis involves the corneal graft clarity. A clear graft was seen in 23–81% of eyes following treatment of PK infectious keratitis.¹⁰ In this case series, only one patient (11.1%) had a clear graft following treatment of post-PK infectious keratitis. Three patients (33.3%) in this case series had graft replacements, which aligns with the report that regrafts are performed in 4.5–53% of cases following post-keratoplasty infectious keratitis.¹⁰ In addition, one patient (11.1%) developed endophthalmitis. In the literature, endophthalmitis occurred as a complication in 1–13% of cases after post-PK infectious keratitis.¹⁰ The percentage of patients in this case series that developed complications related to corneal perforation, epithelial defects, graft replacements, and endophthalmitis were comparable to those patients that had post-keratoplasty infectious keratitis complications without the association of contact lenses.

There were many limitations in this case study. One limitation was the small sample size. Also, the study did not include contact-lens associated infections for patients that wore contact lenses after PK for a short duration of time (< 2 weeks). Finally, the study was not comparative and there was no identification of a causative relationship as many factors, in addition to contact lens usage, may have contributed to the development of infectious keratitis following PK.

In conclusion, contact-lens-associated infectious keratitis following PK is a serious condition associated with high rates of complications. Fungal keratitis occurred more than it was previously reported in the literature in patients without the use of contact lens. Therefore, it is recommended that patients with complex ocular histories who wear contact lenses following PK should have appropriate follow-up and be closely monitored for signs of infection and inflammation as many factors can contribute to the development of infection.

Acknowledgements: none

Conflict of Interest Statement: There are no conflicts of interests to disclose.

Disclosure of Funding: The University of Minnesota Department of Ophthalmology and Visual Neurosciences funded the data retrieval which was performed by the Clinical and Translational Science Institute.

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Clinical Outcomes of Infectious Keratitis Associated with Contact Lens Wear Following Penetrating Keratoplasty: A Case Series

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