Donor Rim Research Articles

Partial DMEK Donor Removal as a Successful Treatment of Donor-Related Fungal Keratitis

Abstract: An 84-year-old woman with Fuchs dystrophy underwent uncomplicated Descemet membrane endothelial keratoplasty in her right eye (OD). Donor rim culture returned positive for Candida albicans with no signs of clinical infection until postoperative week (POW) 14 when the patient noted new eye pain and photosensitivity in the OD. Examination revealed 3+ cells without hypopyon and 2 infiltrates localized to a small peripheral area of previously noted clinically insignificant inferior donor graft scrolling. Anterior chamber tap of the OD was performed, which showed no fungal growth. The patient was administered topical fortified voriconazole 1% 6 times a day and oral voriconazole 200 mg twice a day. On day 3, the infiltrate enlarged, and intracameral amphotericin (0.15 mg/mL, 0.1 cc) was injected. On day 6 with progression of the infiltrate, a partial donor descemetorhexis to remove the infiltrate and intracameral injection of voriconazole (0.25 mg/mL, 0.1 cc) were performed. Culture from the partially removed graft was positive for C. albicans. Vision improved to logMAR 0.18 (Snellen 20/30) with no evidence of recurrence to postoperative month 10. To the best of our knowledge, this is the first case of late-onset Candida interface keratitis successfully treated with a partial descemetorhexis.

The Prevalence of Positive Donor Corneoscleral Rim Culture and its Association with Ocular Infection After Transplantation.

The aim of the study was to determine the prevalence of positive corneoscleral donor rim cultures and to report keratitis and endophthalmitis after keratoplasty. Eye bank records and medical records of patients who underwent keratoplasty between September 1, 2015, and December 31, 2019, were retrospectively reviewed. Patients who had routine donor-rim culture taken during surgery and followed up for at least 1 year in the post-operative period were included in the study. A total of 826 keratoplasty procedures were performed. A total of 120 (14.5%) cases had a positive donor corneoscleral rim culture. Positive bacterial cultures were obtained from 108 (13.7%) of the donors. Bacterial keratitis was observed in one patient (0.83% of recipients) who had a positive bacterial culture. Positive fungal cultures were obtained from 12 (1.45%) donors, of whom one (8.33% of recipients) developed fungal keratitis. Endophthalmitis was observed in one patient whose culture result was negative. Both bacterial and fungal culture results were similar in penetrating and lamellar surgical procedures. Although the donor corneoscleral rims have a high positive culture result, the rate of bacterial keratitis and endophthalmitis is low, the risk of infection is high in patients with a fungal positive donor rim. Closer follow-up of patients with fungal positive donor corneo-scleral rim result and initiation of aggressive antifungal treatment when infection occurs will be beneficial.

Post-Descemet's membrane endothelial keratoplasty Pseudomonas graft infection

To report evaluation and management of graft-host interface keratitis post-Descemet's membrane endothelial keratoplasty (DMEK). A 70-year-old lady with pseudophakic bullous keratopathy who underwent DMEK and developed interface interstitial keratitis on the first postoperative day. Cultures of corneal button revealed gram-negative bacilli (Pseudomonas aeruginosa). Prompt surgical intervention in the form of removal of donor Descemet's membrane and targeted antibacterial therapy helped in the complete resolution of infection. Descemet's stripping endothelial keratoplasty (DSEK) was performed postresolution of infection which yielded a good visual outcome for the patient. Donor rim culture helps immensely in identifying organisms in cases presenting in the early postoperative period.

Comparison of Graft Outcomes Reusing Original Intermediate-Term Cold Storage Solution for Entire Corneal Donor Storage Period With Exchanged Fresh Storage Solution After Donor Preparation in the Cornea Preservation Time Study.

The purpose of this study was to evaluate outcomes of Descemet stripping automated endothelial keratoplasty comparing exchange with fresh intermediate-term cold storage solution after lenticule preparation versus reuse of the original solution in the Cornea Preservation Time Study. In the Cornea Preservation Time Study, 508 donor corneas had lenticules prepared by the eye bank with fresh solution exchange (Fresh group) and 283 with reuse of the original solution (Original group). Storage time for all donors was ≤11 days. Graft success rates, central endothelial cell loss at 3 years, and frequency of positive donor rim cultures were compared between the 2 groups. The 3-year graft success rate (95% confidence interval) was 93.4% (90.7%-95.3%) in the Fresh group and 95.2% (91.8%-97.2%) in the Original group (adjusted hazard ratio for graft failure = 0.64, 95% confidence interval, 0.33-1.24, P = 0.19). The mean percentage endothelial cell loss was significantly greater in the Fresh group versus Original group (45% ± 22% vs. 38% ± 20%, respectively, P = 0.004). Cultures were positive in 4 (1.5%) of 267 donor rims (3 fungal and 1 bacterial) in the Fresh group and in 4 (2.5%) of 158 in the Original group ( P = 0.57). There were 2 postoperative infections in the Original group and none in the Fresh group. The use of the original intermediate-term cold storage solution did not reduce the 3-year graft success rate compared with exchanging with fresh solution after lenticule preparation for Descemet stripping automated endothelial keratoplasty, while the frequency of positive donor rim cultures did not significantly differ between groups.

The impact of amphotericin B-fortified preservation media on donor rim cultures and posttransplant infection.

To determine the impact of amphotericin B supplementation to donor cornea preservation solutions on the rates of positive donor rim fungal cultures and postkeratoplasty fungal infections. This was a retrospective analysis of cases undergoing corneal transplantations at a single tertiary referral center from 2016 to 2021. Patients undergoing corneal transplantations with and without amphotericin B supplementation to the storage media were reviewed for donor rim culture results and postoperative infection. The primary outcome measures were positive donor rim fungal culture results and postkeratoplasty fungal infection. A total of 1238 corneal transplants were analyzed. Of these, 849 were stored in preservation solution without amphotericin B, while 389 had amphotericin B included. There was a lower incidence of positive donor rim fungal cultures in cases with amphotericin B supplementation (1.8%) compared to the cases without amphotericin B (2.9%), although this difference was not statistically significant (P = 0.24). Of the 389 cases with amphotericin B supplementation, one (0.25%) went on to develop clinically significant infection, while three of 849 (0.35%) cases without amphotericin B developed infection. The sample size was too small to determine the effect of amphotericin B on the incidence of postkeratoplasty fungal infection. The addition of amphotericin B to donor cornea preservation solution resulted in a downward trend of positive donor rim fungal cultures and postkeratoplasty fungal infections, although these differences did not reach statistical significance. Further studies with larger sample sizes are necessary to appropriately determine the impact of amphotericin B supplementation in the storage solution on positive donor rims and postkeratoplasty fungal infections.

Effect of Increasing Povidone-Iodine Exposure on Corneal Epithelium and Impact on Donor Rim Cultures.

The purpose of this study was to assess the effect of a second povidone-iodine (PVP-I) application at the time of donor tissue recovery on overall tissue quality and to analyze the rate of positive fungal and bacterial rim cultures before and after implementing increased PVP-I exposure. The left cornea was recovered after a single application of PVP-I, while the right cornea was recovered after double PVP-I application in research-consented donors. The epithelial cell death rate was estimated using viability assay in corneal whole mounts under 10× objective (n = 5). Clinical characteristics of epithelium, stroma, and endothelium; positive rim culture rate; and incidences of infectious postoperative adverse reactions were compared for a period of 14 months before and after implementation of increased PVP-I protocol. The average epithelial cell death rate was unaltered between single and double PVP-I exposure groups. We observed a modest 10% increase in the number of tissues with mild edema after implementation of increased PVP-I exposure. Nonetheless, the percentage of tissues with moderate or severe edema was unaltered. The average positive rim culture rate decreased from 1.17% to 0.88% (P = 0.075) after implementation of the double PVP-I soak procedure. There has been only one report of infectious postoperative adverse reactions since this procedure change. By contrast, there were 5 reports for a period of 14 months before implementation of this protocol. These results indicate that new donor preparation methods with an additional 5 minutes of PVP-I exposure do not affect tissue quality, reduce positive rim cultures, and lead to lower incidence of postoperative infection.

Incidence and Outcomes of Transplant of Infected Donor Corneal Tissues in a Tertiary Hospital in Saudi Arabia.

Purpose: The aim of this study is to assess donor rim culture results and predict ocular infections after corneal transplantation to determine the relationship between positive corneoscleral rim cultures and post-keratoplasty infection.Design: This is a retrospective study.Methods: The microbiology results of positive donor rim culture and clinical outcomes of all contaminated grafts at Dhahran Eye Specialist Hospital (DESH) in the Eastern Region of Saudi Arabia between October 2016 and February 2020 were reviewed.Results: A total of 684 corneal transplantation procedures were performed at DESH during this period. Routine donor rim cultures were done for all cases with six positive cases (0.88%). There were five positive fungal donor rim cultures (0.73%), and one corneal rim was positive for both bacterial and fungal cultures (0.15%). Among these six patients, two patients (33.33%) who received graft positive with candida developed an infection. Both cases required further interventions but were unsuccessful and eventually ended up with re-grafting.Conclusion: In the sample collected, positive fungal contamination was more frequent than bacterial contamination, and the incidence of bacterial infection is relatively low compared to that of fungal infection due to contaminated grafts. Despite the limitations of our study, we support routine corneoscleral rim culture and to start prophylactic antifungal treatment in response to positive donor fungal rim culture.

The Role of Corneal Donor Rim Fungal Cultures: Pro Side.

Fungal infection after corneal transplantation is a rare but potentially devastating complication. It is of paramount concern for transplant surgeons and the eye banking community. The value of universal corneal rim cultures for keratoplasty remains controversial. In 2016, The Eye Bank Association for America reported an increasing trend in the incidence of post keratoplasty fungal infections and a higher incidence of post keratoplasty [penetrating keratoplasty and endothelial keratoplasty (EK)] fungal endophthalmitis cases. This increasing trend in rate over time from previous Eye Bank Association for America reports was disproportionately associated with EK and Candida species. Additionally, several studies confirmed a high correlation between positive corneoscleral donor rim fungal cultures and postoperative infections, and a higher risk to the mate eye of a cornea that had the positive fungal corneal rim culture and developed an infection. Positive fungal donor rim cultures-especially in the setting of interface keratitis after EK surgery-can raise the index of suspicion for a fungal cause and may help direct therapy, especially in the early stages, where the symptoms and signs of spread may not be obvious and obtaining direct cultures is inherently difficult without surgical intervention.

Incidence of Fungal Infection in Positive Donor Rim Cultures after Corneal Transplantation

ABSTRACT Purpose To determine the clinical outcomes of corneal transplant patients that had positive rim cultures for fungi. Methods Retrospective study. Results Of 1276 rim cultures obtained between 2009 and 2019, 16 were positive for fungus (incidence of 1.25%). Clinical data were available for 12 patients. Candida and Cladosporium species were the most common organisms. Recipient ages ranged from 51 to 86 (median age 69 years; 9 males, 7 females). The most common surgery was Endothelial Keratoplasty (n = 8). There were no instances of fungal keratitis or endophthalmitis. Three patients were treated with prophylactic antimycotics. One patient developed bacterial keratitis. One patient had a varicella zoster virus reactivation without corneal involvement. Conclusions This study adds to the growing data on the low rate of fungal keratitis and endophthalmitis after a corneal transplant, even in the case of positive rim cultures. This study also suggests that positive rim cultures do not advance the risk of postoperative fungal infection in the recipient.

Role of Antifungal Prophylaxis After Receipt of a Positive Donor Rim Fungal Culture: The Case for Treatment.

Role of Antifungal Prophylaxis After Receipt of a Positive Donor Rim Fungal Culture: The Case for Treatment.

Incidence and outcome of transplantation of fungal-culture-positive donor corneoscleral tissue in optical keratoplasty.

This study aims to determine the incidence of fungal-culture-positive corneoscleral donor rim in patients undergoing keratoplasty and evaluate clinical outcomes of eyes that received these contaminated donor tissues. Patients who had optical keratoplasty between 2006 and 2016 and were found to have fungal-culture-positive donor rim were included. Microbiological and eye bank records were reviewed to determine the incidence of positive fungal rim cultures. Data were collected on visual and clinical outcomes. The main outcome measures were fungal-culture-positive donor rim and development of fungal keratitis or endophthalmitis post keratoplasty. Long-term clinical outcome and associated complications were the secondary outcome measures. Out of 9620 cases of corneal transplants, 145 (1.5%) had fungal-culture-positive donor rim. Candida was the most common organism, cultured in 127 (87.6%) cases. There were no cases of postoperative fungal keratitis or endophthalmitis. Median follow-up was 4.8years (interquartile range 3.8-7.2years). Only eight cases (5.5%) received prophylactic antifungal treatment. There were 34 (23.4%) cases of rejection, 13 (8.9%) developed glaucoma, and 7 (4.8%) developed late bacterial keratitis. At last follow-up, best corrected visual acuity was 20/60 or better in 88 cases (60.7%) and 115 eyes (79.3%) had a clear graft. The incidence of fungal-culture-positive donor rim is extremely low. The risk of developing fungal keratitis or endophthalmitis in patients who received contaminated donor tissue was almost negligible. Further studies are warranted to prove whether prophylaxis or adding amphotericinB in Optisol-GS confers any added benefit.

The Role of Antifungal Prophylaxis After Receipt of a Positive Donor Rim Fungal Culture: The Case for Not Routinely Treating Prophylactically.

Studies conducted in the United States suggest that 1% to 2% of corneal donor rims culture positive for fungus; the fungal agent is usually Candida, and the risk of an endothelial keratoplasty recipient developing an intraocular fungal infection is approximately 7% (1 in 15) if the donor rim was culture-positive. Routine culturing of corneal donor rims is useful because a positive fungal culture alerts the surgeon to carefully monitor the keratoplasty recipient for any signs of fungal infection. However, routine implementation of antifungal prophylaxis on receipt of a positive culture is problematic because there is a lack of definitive data regarding the optimal route of administration, necessary duration of prophylaxis, and relative efficacy of different antifungal agents. The use of topical prophylaxis alone has not been proven to be effective, and the systemic agents that are effective against Candida typically involve an azole, which has many side effects, including liver toxicity and potential interactions with other drugs. The data suggest that routine antifungal prophylaxis would needlessly expose 14 patients to systemic side effects for each person who would directly benefit. Treatment of postkeratoplasty fungal infection typically involves graft replacement, but selective removal of the involved area(s) has been used successfully with Descemet membrane endothelial keratoplasty.

The Role of Donor Rim Fungal Cultures.

Culturing all donor rims for fungus makes no sense. Only 1% of all cultures will be positive, and of those positive cultures, only 6% will also have a clinical infection. Prophylactically treating all positive cultures means 94% of patients will be treated unnecessarily. Fungal cultures do not reliably direct specific medication choice, and fungal infections of the interface in endothelial keratoplasty and deep anterior lamellar keratoplasty are nearly impervious to medical therapy. Suspected fungal infections of the deep stromal interface should be treated expeditiously with penetrating keratoplasty before peripheral spread or endophthalmitis occur.

A Cluster of Corneal Donor Rim Cultures Positive for Achromobacter Species Associated With Contaminated Eye Solution.

To investigate a cluster of corneoscleral rim cultures positive for Achromobacter species over a 6-month period at Massachusetts Eye and Ear. An increased rate of positive corneal donor rim cultures was noted at Massachusetts Eye and Ear between July and December 2017. Positive cultures were subjected to identification and antimicrobial susceptibility testing by phenotypic (MicroScan WalkAway) and genotypic (16S rDNA sequencing) methods. Samples of the eye wash solution (GeriCare) used in the eye bank were also evaluated. Antimicrobial activity of Optical-GS against Achromobacter spp. at 4°C and 37°C was assessed by time-kill kinetics assay. Of 99 donor rims cultured, 14 (14.1%) grew bacteria with 11 (78.6%) due to uncommon nonfermenting Gram-negative bacilli. These had been identified by standard automated methods as Achromobacter (n = 3), Alcaligenes (n = 3), Ralstonia (n = 2), Pseudomonas (n = 2), and Stenotrophomonas (n = 1). Eight of these 11 isolates were subsequently available for molecular identification, and all were identified as Achromobacter spp. Six bottles of eyewash solution were evaluated and were positive for abundant Achromobacter spp. (3.4 × 105 ± 1.1 CFU/mL). Optisol-GS had no bactericidal activity against Achromobacter spp. at 4°C after 24-hour incubation but was bactericidal at 37°C. None of the patients who had received the contaminated corneas developed postoperative infection. An eyewash solution arising from a single lot was implicated in the contamination of donor rims by Achromobacter spp. The isolates were able to survive in the Optisol-GS medium at the recommended storage temperature. This highlights the need to continue improving protocols for tissue preparation and storage.

Queratoplastia penetrante temprana después de queratitis fúngica de la interface en la queratoplastia endotelial de la membrana de Descemet

In this case-report we describe the first reported case of early-onset fungal interface keratitis (IK) after Descemet Membrane Endothelial Keratoplasty (DMEK) successfully treated with penetrating keratoplasty (PK) during the active stage of infection. A patient with graft failure after Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) was operated on with DMEK. Donor rim culture and broth were positive for Candida albicans. Several interface infiltrates were confirmed and localized using anterior segment optical coherence tomography. Three days after diagnosis, observing clear signs of intraocular infection, the graft was removed with simultaneous washed-up of anterior chamber with fluconazole 1% followed by a PK and intrastromal corneal injections of fluconazole. A best-corrected visual acuity of 20/20 was achieved. This case highlights the importance of analysing every donor rim and broth, despite the patient doesn’t show any symptoms or signs during the post-operative period. PK is a viable treatment option in early-onset interface keratitis.

Test-retest reproducibility of atomic force microscopy measurements of human trabecular meshwork stiffness

Purpose: The purpose of the present study was to quantify test-retest reproducibility of measurements of stiffness of the human trabecular meshwork (HTM) by atomic force microscopy (AFM).
 Methods: Eleven 40 μm radial limbal cryostat sections from a fresh human donor rim were mounted on charged slides and rehydrated at room temperature. Stiffness at four TM locations (anterior to posterior along Schlemm’s canal) was measured by AFM. At each location, a 6 x 6 grid was sampled. Indentation points were evenly distributed over a 20 μm x 20 μm area, with a rate of one load/unload cycle per second. Measurements were then repeated for calculation of test-retest variability.
 Results: The test-retest coefficients of variation for the four measurement locations (anterior to posterior) were 24.39, 25.28, 12.74, and 14.26%, respectively, with a notable drop in the two posterior locations compared to the anterior. The test-retest coefficient for the sections was 19.17%. For the entire eye, the test-retest coefficient of variation for the measurement of the TM stiffness was 17.13%. Young’s moduli consistently decreased from anterior to posterior location.
 Conclusions: Wide regional variation suggests that single value does little to fully describe the complex array of TM stiffness levels within the eye, and future studies of TM stiffness assessed by AFM should include multiple tissue samples from each eye, with documentation of the anterior-posterior location of each measurement.

Acute interface infectious keratitis with multidrug resistant Klebsiella and Escherichia Coli following deep anterior lamellar keratoplasty

Acute interface infectious keratitis (AIIK) is a rare and devastating complication following lamellar keratoplasty. Here, we report a case of AIIK following deep anterior lamellar keratoplasty (DALK) caused by double gram-negative bacilli and required urgent therapeutic penetrating keratoplasty (TPK). Microbiology revealed co-infection with Klebsiella and E. Coli sensitive only to colistin. Donor rim culture also grew Klebsiella. TPK was successful in controlling the infection and the patient responded to topical fortified amikacin and ciprofloxacin. Since optical quality tissue was used, the patient regained 20/40 vision postoperatively. This report highlights that immediate TPK and intense antimicrobial therapy can salvage these eyes with good visual outcome.

Increasing Povidone-Iodine Exposure in Endothelial Keratoplasty Tissue Processing and Fungal Infection Impact.

To evaluate the effect on donor rim cultures and postoperative infections of doubling the povidone-iodine exposure time during corneal tissue recovery before its use in keratoplasty. Consecutive donor cornea recoveries were evaluated for positive donor corneal rim cultures and postoperative infections before and after a protocol change of doubling the exposure time of povidone-iodine during donor preparation. In 631 consecutive cornea donor recoveries, 18 (2.9%) had positive fungal rim cultures and 41 (6.5%) had positive bacterial rim cultures. Three (0.48%) developed postoperative fungal infections, and no bacterial infections occurred. After doubling the povidone-iodine exposure time during the recovery process, 725 consecutive corneas were reviewed. Four (0.6%) had positive fungal rim cultures, and 29 (4.0%) had positive bacterial rim cultures. No postoperative fungal or bacterial infections occurred. No noticeable increase in epithelial toxicity developed between the 2 groups. Increasing the povidone-iodine exposure time during the donor cornea recovery process decreased the rate of positive donor corneal rim fungal cultures (P = 0.001), positive donor corneal rim bacterial cultures (P = 0.04), and postoperative fungal infections (P = 0.06).

Interface infectious keratitis after anterior and posterior lamellar keratoplasty. Clinical features and treatment strategies. A review

Interface infectious keratitis (IIK) is a novel corneal infection that may develop after any type of lamellar keratoplasty. Onset of infection occurs in the virtual space between the graft and...

Interface Fungal Keratitis After Descemet Stripping Automated Endothelial Keratoplasty: A Review of the Literature With a Focus on Outcomes.

To examine the management and associated outcomes of reported cases of interface fungal infection after Descemet stripping automated endothelial keratoplasty (EK). A literature review identified reports of interface fungal infection after Descemet stripping automated EK. Data retrieved from the same included patient demographics, surgical procedure undertaken, donor rim culture result, clinical course, and outcome. A review of the relevant literature was also conducted. Twenty-four cases of interface fungal infection after Descemet stripping automated EK were analyzed. Mean age of those affected was 66 years with range 52 to 85 years. Interface fungal infection after Descemet stripping automated EK was noted at a mean of 49.2 days postoperatively. Candida species were the causative infection in 79% cases. Penetrating keratoplasty was eventually performed in 79% of cases. The mean posttreatment best-corrected visual acuity was 0.44 logMAR. Penetrating keratoplasty is frequently required to eliminate interface fungal infection after Descemet stripping automated EK. A satisfactory visual outcome is usually achieved.