Infections with EK procedures rising

Descemet’s stripping automated endothelial keratoplasty (DSAEK) appears to have a higher risk of postoperative fungal infections (predominantly Candida) when compared to penetrating keratoplasty (PK).

Donald T.H. Tan, FRCS, FRCOphth, pointed out that infectious keratitis and endophthalmitis do occur after DSAEK-fungal, bacterial, and viral.

“The higher risk for postop fungal infections seems to relate to donor contamination, lack of anti-fungal prophylaxis in donor storage media, and repeated warming cycles during DSAEK donor tissue processing in eye banks,” said Dr. Tan, Singapore National Eye Centre.

As a result, Dr. Tan said donor rim fungal cultures are recommended for endothelial keratoplasty (EK), and prophylaxis with antifungal therapy is recommended for EK patients with positive donor cultures for fungus.

What the literature says

The first fungal infection occurring after EK was published in 2003,¹Dr. Tan said, well before the days of DSAEK.

“Dr. Massimo Busin’s case happened to be a Mycobacterium chelonae interface infection,” Dr. Tan said, that was successfully treated with clarithromycin.

A seminal meta-analysis of endophthalmitis after PK showed that, on average, 14% of donor rims have a positive culture, and of those, 0.2% developed endophthalmitis.²In that analysis, there were 21 concordant cultures, both donor and recipient had the same cultures and the authors specified that there were 10 cases of Candida endophthalmitis.

“In positive donor rim cases in this analysis, after a PK the risk of endophthalmitis is about 1%, and the risk of fungal endophthalmitis is about 3%,” Dr. Tan said.

Since its introduction in 1997, DSAEK has rapidly gain acceptance among corneal surgeons, becoming “the most common form of EK performed today,” Dr. Tan said, but the first published case reports did not appear until 2009 (although the cases occurred in 2007), and both were cases of Candida, with different outcomes.^3,4

In the first case, an 80-year-old presented with pseudophakic bullous keratitis that was eventually diagnosed as Candida albicans and the eye required enucleation. In the second case, two cases of donor-host transmission of C.albicans post-DSAEK, and both cases were from the same donor.

“In this case, both eyes were saved,” Dr. Tan said, but that prompted his own case of fungal endophthalmitis from venting incisions.⁵

“I had to re-open up the previous venting incisions in a repeat DSAEK case,” Dr. Tan said. “They remained open and, therefore, fungal infection through these opened vents occurred.”

In this case, it was Candida parapsilosis and “there are now about 20 reported cases in 15 articles.”

While most of the fungal infections are Candida species, the severity ranges. Risk factors include donor contamination, and a “very important aspect” is interface sequestration, which can hinder the penetration of antifungal treatments.

Bacterial, fungal infections

Bacterial, fungal infections

Over a five-year period, 14 cases of bacterial infections during EK surgeries were reported in nine articles, with causes linked to Pseudomonas, Staphylococcus aureus, microbacterial, and Streptococcus endocardium, with the majority being Pseudomonas and S. aureus.

“Other than the risk factors for fungi, some also have suggested contact lens wear combined with steroid use, which kind of makes sense,” Dr. Tan added.

The Eye Bank Association of America (EBAA) reported in 2013⁶that from 2007 to 2010, “there were 31 cases of fungal infections, both keratitis and endophthalmitis, and that made it 1.4 cases for 10,000 transplants,” Dr. Tan said.

Fungal infections were “commonly reported after EK. It was 0.022% versus 0.012%, but the difference failed to reach statistical significance,” he pointed out.

In 2015, the EBAA found that in 2013, there were 26 cases of fungal infections, making the infection rate of 0.039%, which was statistically significantly higher (p < 0.01). The majority of these were endophthalmitis and mostly Candida, (16 cases, 62%).

Additionally, over half of the EK cases were from precut tissue performed in the eye bank. “With eye bank preparation, the risk was 0.11% compared to surgeon preparation in the OR, which was 0.01%, and again this reached statistical significance,” Dr. Tan explained. 

Warming tissue, other causes

Dr. Tan said the increasing incidence of postoperative fungal infection following DSAEK and the high incidence with eye bank preparation should be confirmed, the causes identified, and the issues addressed.

The effect of warming donor corneas to room temperature (which occurs frequently in EK due to the need for image assessment of the endothelium as well as pre-cutting of tissue) may play a role.

Fungal growth is static during refrigeration, “but during the warming period, Candida started to grow, all three Candida subspecies, and then the tissue is stored at room temperature,” Dr. Tan said. Tu, et al further showed the number of warming cycles is equally important; with each one-hour warming cycle, a marked increase in Candida occurs.⁷

“There is a significant need for antifungal supplementation,” Dr. Tan said.

Over the past few years, there has been a reported increase in post-DSAEK cytomegalovirus (CMV) endotheliitis, mostly in Asian countries, but “several cases” have been reported in the United States.

“The diagnostic dilemma is that it looks very similar to an allograft rejection episode,” Dr. Tan said, and diagnosis requires identification of CMV antigen by an AC tap; the treatment is to stop or reduce topical steroids, and to start topical ganciclovir and oral valganciclovir with “a high index of suspicion warranted for these cases.”

Vigilance about potential infections in the EK setting will help mitigate the potential devastating effects, and hopefully lower the incidence even further.

References

1. Busin M. A new lamellar wound configuration for penetrating keratoplasty surgery. Arch Ophthalmol 2003;121(2):260-5.

2. Wilhelmus KR, Hassan SS. The prognostic role of donor corneoscleral rim cultures in corneal transplantation. Ophthalmology 2007;114(3):440-5.

3. Koenig SB, Wirostko WJ, Fish RI, Covert DJ. Candida keratitis after descemet stripping and automated endothelial keratoplasty. Cornea 2009;28(4):471-3.

4. Kitzmann AS, Wagoner MD, Syed NA, Goins KM. Donor-related Candida keratitis after Descemet stripping automated endothelial keratoplasty. Cornea 2009;28(7):825-8.

5. Chew AC, Mehta JS, Li L, et al. Fungal endophthalmitis after descemet stripping automated endothelial keratoplasty--a case report. Cornea 2010;29(3):346-9.

6. Aldave AJ, DeMatteo J, Glasser DB, et al. Report of the Eye Bank Association of America medical advisory board subcommittee on fungal infection after corneal transplantation. Cornea 2013;32(2):149-54.

7. Tu EY. The Effect of Repeated Warming Cycles of Corneal Storage Media on Fungal Infection Risk in Endothelial Keratoplasty. Presented at: Cornea Subspecialty Day, American Academy of Ophthamology. Las Vegas, NV. November 13, 2015.

Donald T.H. Tan, FRCS, FRCOphth

E: donald.tan.t.h@singhealth.com.sg

This article was adapted from Dr. Tan’s presentation that he delivered at the Cornea Subspecialty Day prior to the 2016 American Academy of Ophthalmology annual meeting.