Elvin H. Yildiz

Update on fungal keratitis from 1999 to 2008.

Purpose: To report trends in fungal keratitis from a single institution between 1999 and 2008. Methods: Retrospective chart review of the patients presenting to the cornea service with fungal keratitis from April 1999 to December 2008. Results: Seventy-eight eyes of 76 patients were identified. The most common predisposing factors included contact lens use (35.9%), trauma (21.8%), and history of penetrating keratoplasty (15.4%). There was a significant increase in the rate of contact lens-related Fusarium infections over time, which peaked in 2005 and 2006 (P = 0.021). Almost 40% of fungal keratitis cases [11 of 28 eyes (39.3%)] were soft contact lens-related Fusarium infections in 2005 and 2006, and this decreased to less than 10% [2 of 25 eyes (8%)] in 2007 and 2008. The odds of having a contact lens-related Fusarium infection in 2005-2006 compared with 2007-2008 was 4.40 (95% confidence interval of 0.60-32.50) (P = 0.178). Despite the decrease in contact lens-related Fusarium infections, the number of fungal infections remained elevated in 2007 (10 eyes) and 2008 (14 eyes), including contact lens-related infections (3 in 2007 and 6 in 2008). Conclusions: A definite increase in the number of fungal keratitis cases began in 2004 and continued through 2006 during the Fusarium outbreak associated with ReNu with MoistureLoc. Despite the decrease in contact lens-related Fusarium infections, the overall number of fungal keratitis cases remained high through 2008. Fungal keratitis was more often associated with contact lens use than with trauma in this time.

In vitro susceptibility patterns of methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus corneal isolates to antibiotics.

Purpose: To determine the in vitro susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRCNS) isolates to various antibiotics. Methods: All cases of bacterial keratitis caused by Staphylococcus species during 2006 and 2007 were identified. The isolates were divided according to species and susceptibility to methicillin into 4 groups: methicillin-susceptible S. aureus, methicillin-susceptible coagulase-negative Staphylococcus, MRSA, and MRCNS. Routine susceptibility testing for Staphylococcus species to methicillin and 19 other antibiotics was performed using the MicroScan POS Breakpoint Combo Panel Type 20. Results: One hundred fifty-seven isolates were identified. Forty isolates were S. aureus, including 21 MRSA, and 117 isolates were coagulase-negative Staphylococcus, including 29 MRCNS. All MRSA isolates were susceptible to gentamicin, linezolid, rifampin, tetracycline, and vancomycin and were resistant to penicillin, cefazolin, cefepime, azithromycin, erythromycin, and ofloxacin. Ninety percent of MRSA isolates were resistant to fourth-generation fluoroquinolones. All MRCNS isolates were susceptible to vancomycin, chloramphenicol, linezolid, and rifampin and were resistant to penicillin, cefazolin, cefepime, and azithromycin. Sixty-five percent of the MRCNS isolates were susceptible to fourth-generation fluoroquinolones and gentamicin. Conclusions: All MRSA and MRCNS isolates were sensitive to vancomycin, linezolid, and rifampin. MRSA isolates were generally sensitive to gentamicin and tetracycline and resistant to fourth-generation fluoroquinolones. MRCNS isolates were not consistently sensitive to gentamicin, tetracycline, or fourth-generation fluoroquinolones.

Steroid-induced intraocular pressure elevation or glaucoma after penetrating keratoplasty in patients with keratoconus or Fuchs dystrophy.

Purpose: The aim of the present study was to evaluate the frequency of steroid-induced intraocular pressure (IOP) elevation and/or glaucoma in patients with keratoconus (KCN) compared with patients with Fuchs endothelial dystrophy after penetrating keratoplasty (PK). Methods: A retrospective review of the medical records of patients with KCN or Fuchs dystrophy, who underwent PK and were examined on the Cornea Service, Wills Eye Institute, was performed. IOP measurements were recorded preoperatively; postoperative first month and maximal IOP measurements between 1 and 3 months, 4 and 6 months, 7 and 12 months, 1 and 2 years, 2 and 3 years, and 3 and 4 years were noted. Steroid-induced IOP elevation and/or glaucoma were grouped into 5 different categories; an increase in IOP of at least 5 or 10 mm Hg over the preoperative baseline and also IOP ≥22, 30, and 40 mm Hg. Addition of glaucoma medications and/or characteristic glaucomatous optic disc and visual field changes were also assessed. Results: A total of 100 patients with KCN and 58 patients with Fuchs dystrophy were included in this study. The overall frequency of steroid-induced IOP elevation after PK was 73% in the KCN group and 60.3% in the Fuchs dystrophy group. The frequency of IOP elevation of at least 5 or 10 mm Hg over the preoperative baseline were 72% and 24% in KCN group and 56.9% and 20.7% in the Fuchs dystrophy group, respectively. The frequency of IOP elevation ≥22 or ≥30 mm Hg was 22% and 6% in the KCN group and 29.3% and 1.7% in the Fuchs dystrophy group, respectively. There was one patient in the KCN group who had IOP >40 mm Hg. There was no difference between the groups in terms of frequency of IOP elevation (P > 0.05 for all). Glaucomatous visual field defect was detected in 4 patients in the KCN group and only one patient in the Fuchs dystrophy group. Despite the maximum medical therapy, 2 patients in the KCN group underwent glaucoma surgery and none in the Fuchs dystrophy group. Conclusion: Steroid-induced IOP elevation or glaucoma after PK is not unusual in eyes with KCN or Fuchs dystrophy. Careful and ongoing observation of IOP throughout the prolonged follow-up period is recommended for these individuals with prompt attention to IOP treatment as indicated.

Clinical outcomes and prognostic factors associated with acanthamoeba keratitis.

Purpose: To describe the clinical characteristics, time of presentation, risk factors, treatment, outcomes, and prognostic factors on a recent series of Acanthamoeba keratitis (AK) treated at our institution. Methods: Retrospective case series of 59 patients diagnosed with AK from January 1, 2004 to December 31, 2008. Of these 59 patients, 51 had complete follow-up data and were analyzed using univariate and multivariate logistic regression analyses performed with “failure” defined as requiring a penetrating keratoplasty (PKP) and/or having (1) best-corrected visual acuity (BCVA) <20/100 or (2) BCVA <20/25 at the last follow-up. A single multivariate model incorporating age, sex, steroid use before diagnosis, time to diagnosis, initial visual acuity (VA), stromal involvement, and diagnostic method was performed. Results: Symptom onset was greatest in the summer and lowest in the winter. With failure defined as requiring PKP and/or final BCVA <20/100, univariate analysis suggests that age >50 years, female sex, initial VA <20/50, stromal involvement, and patients with a confirmed tissue diagnosis had a significant risk for failure; however, none of these variables were significant using multivariate analysis. Univariate analysis, with failure defined as requiring PKP and/or final BCVA <20/25, showed stromal involvement and initial VA <20/50 were significant for failure-only initial VA <20/50 was significant using multivariate analysis. Conclusions: Symptom onset for AK is greatest in the summer. Patients with confirmed tissue diagnosis and female patients may have a higher risk for failure, but a larger prospective population-based study is required to confirm this. Failure is likely associated with patients who present with stromal involvement and patients presenting with an initial BCVA worse than 20/50.

Trends in contact lens-related corneal ulcers at a tertiary referral center.

Purpose: To evaluate the changes and trends in the number and characteristics of contact lens–related ulcers (CLRUs) and to compare the results with those of previously published series at our institution. Methods: Medical records of all patients diagnosed with presumed bacterial corneal ulcers seen at the Cornea Service, Wills Eye Institute, between January 1, 2004, and December 31, 2007, were retrospectively reviewed. Results: Five hundred seven corneal ulcers were identified. Of these, 223 (43.9%) were contact lens (CL) related and 284 (56.1%) were not CL related. The proportion of CLRU showed a significant increase over time (P = 0.003), with significantly greater percentage of CLRU in 2006 and 2007 compared with 2004 (P = 0.004 and P = 0.005, respectively). One hundred thirty-one (58.7%) of the 223 CLRU patients were men. Many CLRUs were vision threatening, with 45.7% (92 of 201) more than 4 mm2 in size, 36.3% (81 of 223) associated with hypopyon, and 46.4% (103 of 222) central or paracentral in location. Pseudomonas aeruginosa was the most frequent agent isolated in CLRUs, found in 75 (63.0%) of 119 positive cultures. Soft daily-wear frequent replacement lenses were the most common lenses associated with corneal ulcers and were used in 68 (33.5%) of 203 cases. There was a history of overnight wear of CLs in more than half of the cases (121 of 223, 54.3%). Of these, 21 (9.4%) were not approved for overnight wear. Conclusions: There was a significant increase in the number of cases of presumed bacterial keratitis associated with soft CL wear over the study period from 2004 to 2007 at our institution. The significant increase in CLRU noted from 1996 to 1999 to 1999 to 2002 reported previously seems to have continued between 2004 and 2007.

Repeat penetrating keratoplasty: indications and prognosis, 1995-2005

Purpose To evaluate the data of penetrating keratoplasty over a 10-year period and to compare indications and outcomes of eyes undergoing single graft with those of eyes requiring regrafting. Methods A total of 652 eyes of 613 patients required single graft (Group I). Sixty-one regrafts were performed on 53 eyes (Group II). The mean follow-up time was 23.4±21.3 months (range 6–132 months). The results were evaluated for the following criteria: primary indications, allograft reactions, graft clarity, final postoperative visual acuity, and complications leading to reduction in vision. Results The most common indication was keratoconus (228 eyes; 35.0%) in Group I, and vascularized corneal scar (12 eyes; 22.6%) in Group II. Allograft reactions occurred in 96 eyes (14.7%) in Group I, and 17 eyes (32.0%) in Group II (p=0.001). At the end of the study period, 76.4% of patients in Group I had entirely clear grafts, whereas 45.3% of patients in Group II had entirely clear grafts (p=0.000). The main causes of corneal graft failure were irreversible allograft reaction, endothelial failure, and graft infection, which were all seen in higher percentage in the regraft group. A best-corrected visual acuity of 20/100 or better was achieved in 377 eyes (57.8%) in Group I and 11 eyes (20.7%) in Group II (p=0.000). Conclusions The complications of repeated surgery may reduce final graft clarity and visual acuity; the disease process necessitating regrafting may carry a poorer prognosis for sight.

Evaluation of a new tear osmometer for repeatability and accuracy, using 0.5-microL (500-Nanoliter) samples.

Purpose: To evaluate the repeatability and accuracy of a new tear osmometer that measures the osmolality of 0.5-μL (500-nanoliter) samples. Methods: Four standardized solutions were tested with 0.5-μL (500-nanoliter) samples for repeatability of measurements and comparability to standardized technique. Two known standard salt solutions (290 mOsm/kg H2O, 304 mOsm/kg H2O), a normal artificial tear matrix sample (306 mOsm/kg H2O), and an abnormal artificial tear matrix sample (336 mOsm/kg H2O) were repeatedly tested (n = 20 each) for osmolality with use of the Advanced Instruments Model 3100 Tear Osmometer (0.5-μL [500-nanoliter] sample size) and the FDA-approved Advanced Instruments Model 3D2 Clinical Osmometer (250-μL sample size). Results: Four standard solutions were used, with osmolality values of 290, 304, 306, and 336 mOsm/kg H2O. The respective precision data, including the mean and standard deviation, were: 291.8 ± 4.4, 305.6 ± 2.4, 305.1 ± 2.3, and 336.4 ± 2.2 mOsm/kg H2O. The percent recoveries for the 290 mOsm/kg H2O standard solution, the 304 mOsm/kg H2O reference solution, the normal value-assigned 306 mOsm/kg H2O sample, and the abnormal value-assigned 336 mOsm/kg H2O sample were 100.3, 100.2, 99.8, and 100.3 mOsm/kg H2O, respectively. Conclusions: The repeatability data are in accordance with data obtained on clinical osmometers with use of larger sample sizes. All 4 samples tested on the tear osmometer have osmolality values that correlate well to the clinical instrument method. The tear osmometer is a suitable instrument for testing the osmolality of microliter-sized samples, such as tears, and therefore may be useful in diagnosing, monitoring, and classifying tear abnormalities such as the severity of dry eye disease.

Third or greater penetrating keratoplasties: indications, survival, and visual outcomes.

Purpose: The purposes of this study were to report the indications, graft survival, risk factors for graft failure, and visual outcomes for third or greater penetrating keratoplasties (PKP). Methods: Six years of Wills Eye Institute Cornea Service charts (2000-2005) were retrospectively reviewed to identify all patients who had undergone three or more PKPs. Graft survival rates by initial diagnosis and risk factors for graft failure were analyzed. Results: Forty-five patients who had three or more PKPs were identified. The total number of grafts identified in these 45 patients was 152, including 45 third PKPs, 11 fourth, three fifth, two sixth, and one seventh. The most common indication for the initial PKP was pseudophakic bullous keratopathy in 18 of 45 patients (41%) followed by Fuchs dystrophy (seven of 45 patients [16%]) and stromal dystrophies (five of 45 patients [11%]). Approximately half of third grafts (24 of 45 [53%]) and one fourth of fourth grafts (three of 11 [27%]) survived at the last follow-up visit with a median follow up of 4.3 years for the third grafts and 8.4 years for the fourth grafts. One-, 2-, and 5-year graft survival rates were 89%, 78%, and 53% for the third grafts and 73%, 73%, and 64% for the fourth grafts, respectively. The median survival time for the third graft was 12.8 years in Fuchs dystrophy, 5.2 years in herpetic keratitis, 4.0 years in keratoconus, 3.0 years in pseudophakic bullous keratopathy, 2.3 years in iridocorneal endothelial syndrome, and 2.0 years in stromal dystrophies. There is no statistically significant difference between groups (P = 0.46). Risk factor analysis on the third grafts showed that previous glaucoma procedures and corneal neovascularization are statistically significant risk factors for graft failure (P = 0.04 and 0.02, respectively). Conclusion: Over 50% of third and fourth grafts were clear at 5 years postoperatively. Outcomes of third grafts were better in patients with Fuchs dystrophy, keratoconus, and herpetic keratitis. Absence of previous glaucoma surgery and/or corneal neovascularization is associated with better outcomes of multiple PKPs.

Quality of Life in Keratoconus Patients After Penetrating Keratoplasty

PURPOSE To determine vision-related quality of life (QoL) measured with the National Eye Institute Visual Function Questionnaire (NEI-VFQ) in keratoconus (KCN) patients who have undergone penetrating keratoplasty (PK) in 1 or both eyes and to compare the results of our study to those of historical controls. DESIGN Clinical-based, cross-sectional study. METHODS SETTING Wills Eye Institute, Cornea Service, Thomas Jefferson University, Philadelphia, Pennsylvania. STUDY POPULATION This study included 149 consecutive patients who had undergone PK for KCN. INTERVENTION Between June 1, 2008 and December 31, 2008, the NEI-VFQ was administered to 149 patients. The relationship between demographic and clinical factors and NEI-VFQ subscale scores was evaluated. MAIN OUTCOME MEASURE Vision-related quality of life. RESULTS Eighty-three of 149 patients (55.7%) were male. Approximately half of the patients (76/149; 51.0%) had PK in both eyes. Visual acuity with current correction in the better eye was better than 20/40 in 80% of patients (119/149). Our sample had significantly lower (worse) NEI-VFQ scores compared to Collaborative Longitudinal Evaluation of Keratoconus (CLEK) historical control group for the subscales of role difficulties, dependency, driving, and peripheral vision. In general, scores of our sample were between scores of patients with age-related macular degeneration (AMD) category 3 and 4. Patients with visual acuity better than 20/40 (in the better eye) showed significantly higher scores in all subscales except color vision. There was a significant relationship between minimum time since the graft of 5 years or greater and NEI-VFQ overall score better than AMD category 3 (P = .004). CONCLUSION Despite satisfactory results on visual outcome measures obtained after PK, vision-related QoL in KCN patients remains impaired.

Contact Lens Related Quality of Life in Patients With Keratoconus

Objectives: To assess the impact of the different types of contact lenses (CLs) on quality of life (QoL) in patients with keratoconus based on self-reported results from The Contact Lens Impact on Quality of Life (CLIQ) Questionnaire. Methods: Consecutive keratoconus patients who wore CLs (rigid gas permeable [RGP], hybrid or soft toric) at least in one eye were asked to complete the CLIQ questionnaire on the Cornea Service, Wills Eye Institute. Results: A total of 71 patients with a mean age of 42.6 ± 13.1 year were included in the study. One eye of each patient was included in the study. Of these, 40 eyes used rigid gas-permeable lenses, 20 eyes used hybrid lenses and 11 eyes used soft toric lenses. The mean CLIQperson measure was 45.5 ± 8.2 in RGP group, 45.4 ± 7.5 in hybrid group and 48.4 ± 10.5 in soft toric group. There was no significant difference among the three groups in self-reported results from the CLIQ questionnaire (P = 0.8). Conclusions: Subjects with keratoconus who wear RGP, hybrid or soft toric CLs, reported similar contact lens impact on their QoL.