Steven P. Dunn

Transsclerally Sutured Intraocular Lenses in Penetrating Keratoplasty

We reviewed the charts of 114 consecutive patients who underwent penetrating keratoplasty with transscleral fixation of a posterior chamber intraocular lens. Two patients died within three months of follow-up and were excluded from the study. In the remaining 112 patients, follow-up ranged from four to 47 months (mean, 17.2 months). Postoperative visual acuity improved in 95 patients (85%), remained the same in 13 patients (11.5%), and worsened in four patients (3.5%). In 71 patients with at least one year of follow-up, best-corrected visual acuity was 20/40 or better in 17 patients (24%), 20/50 to 20/80 in 25 patients (35%), 20/100 to 20/400 in 17 patients (24%), and counting fingers or worse in 12 patients (17%). Problems with lens decentration, tilt, dislocation, or scleral suture-related infections were minimal. Glaucoma and cystoid macular edema were the most common causes of decreased visual acuity. Four patients (3.6%) developed intraoperative choroidal detachments. Three patients (2.7%) developed rhegmatogenous retinal detachments early in the postoperative course.

Concentrations of levofloxacin, ofloxacin, and ciprofloxacin in human corneal stromal tissue and aqueous humor after topical administration.

Objective: To evaluate the penetration of commercially available levofloxacin 0.5%, ofloxacin 0.3%, and ciprofloxacin 0.3% topical ophthalmic solutions in human corneal stromal and aqueous humor tissues. Methods: A total of 67 patients scheduled to undergo penetrating keratoplasty for treatment of stromal scar or dystrophy, keratoconus, pellucid marginal degeneration, or endothelial disease were enrolled in this prospective, double-blind, 3-center study. To be considered for inclusion, patients had to have an intact corneal epithelium and minimal or no corneal edema (pachymetry < 650 μm). After informed consent was obtained, patients were randomized to receive 1 drop of levofloxacin 0.5%, ofloxacin 0.3%, or ciprofloxacin 0.3% topical ophthalmic solution at approximately 15 and 10 minutes before surgery. Approximately 0.1 mL of aqueous fluid was aspirated by paracentesis through the trephination wound at the onset of surgery, followed by excision of the affected cornea and removal of its epithelium. Specimens were stored frozen at −70°C until assayed by high-performance liquid chromatography. Results: All 3 fluoroquinolones were well tolerated. A total of 65 corneas and 59 aqueous fluid samples were obtained and assayed. The mean ± standard deviation corneal concentrations of ciprofloxacin, ofloxacin, and levofloxacin following a 2-drop administration were 9.92 ± 10.99 μg/g (n = 18), 10.77 ± 5.90 μg/g (n = 23), and 18.23 ± 20.51 μg/g (n = 24), respectively. Although corneal stromal levels were highest in the levofloxacin group, the high degree of interpatient variability prevented demonstration of statistically significant differences when compared with ofloxacin (P = 0.377). In contrast, levofloxacin concentrations were approximately twice as high as ciprofloxacin, and this difference reached statistical significance (P = 0.014). The corresponding aqueous humor concentrations of ciprofloxacin, ofloxacin, and levofloxacin were 0.135 ± 0.231 μg/mL (n = 15), 0.135 ± 0.111 μg/mL (n = 20), and 0.372 ± 0.546 μg/mL (n = 24, P < 0.001 versus ciprofloxacin and ofloxacin). Conclusion: The topical administration of all 3 agents was well tolerated in patients undergoing penetrating keratoplasty. Two drops of levofloxacin 0.5% solution results in a 1.7- to 2.7-fold greater penetration into human corneal stromal and aqueous humor tissues than ofloxacin 0.3% or ciprofloxacin 0.3%. The mean intracorneal concentrations of all three agents following 2 drops exceeds the MIC90 for the majority of pathogens causing bacterial keratitis. Topical levofloxacin appears to offer pharmacokinetic and pharmacodynamic advantages over ofloxacin and ciprofloxacin in terms of enhanced transcorneal penetration; however, clinical comparative trials are needed to confirm these relative advantages.

Retrospective review of graft dislocation rate associated with descemet stripping automated endothelial keratoplasty after primary failed penetrating keratoplasty

Purpose: To report the rate of graft dislocation in patients who underwent Descemet stripping automated endothelial keratoplasty (DSAEK) after a previous penetrating keratoplasty (PKP). Methods: Institutional review board-approved, multicenter, retrospective chart review. Inclusion criteria included: prior failed PKP and subsequent DSAEK. The primary outcomes measured in this study were the presence of a graft dislocation, rate of rebubble, and graft attachment. Additional variables included: presence of a prior glaucoma drainage device, graft-to-host size disparity, number of sutures remaining in PKP, and stripping of the Descemet membrane at the time of DSAEK surgery. Results: Ninety patients (97 eyes) were included in the study. In 31% (30 of 97), the endothelial graft dislocated after surgery. All 30 cases required a rebubble except 1, which reattached spontaneously. Ninety-eight percent (95 of 97) of all grafts remained attached for the duration of the follow-up period. Only 2 eyes (2.2%) required repeat graft. Endothelial grafts dislocated in 67% of patients with glaucoma draining devices. The dislocation rate for grafts larger than the host was 12 of 49 (24%), equal to the host was 3 of 17 (18%), and smaller than the host was 8 of 19 (42%). Dislocations occurred in 5 of 21 (24%) of grafts with sutures remaining and 22 of 76 (29%) of those with all sutures out. Five of 12 (42%) cases of grafts performed without stripping the Descemet had dislocations. Conclusions: The graft dislocation rate in DSAEK procedures after PKP is comparable to that after primary DSAEK cases. Donor grafts that are smaller than the host PKP and the presence of prior glaucoma drainage devices are risk factors for higher rates of graft dislocation.

A multicenter study to map genes for Fuchs endothelial corneal dystrophy: Baseline characteristics and heritability

Purpose: To describe the methods for family and case–control recruitment for a multicenter genetic and associated heritability analyses of Fuchs endothelial corneal dystrophy (FECD). Methods: Twenty-nine enrolling sites with 62 trained investigators and coordinators gathered individual and family information, graded the phenotype, and collected blood and/or saliva for genetic analysis on all individuals with and without FECD. The degree of FECD was assessed in a 0 to 6 semiquantitative scale using standardized clinical methods with pathological verification of FECD on at least 1 member of each family. Central corneal thickness was measured by ultrasonic pachymetry. Results: Three hundred twenty-two families with 330 affected sibling pairs with FECD were enrolled and included a total of 650 sibling pairs of all disease grades. Using the entire 7-step FECD grading scale or a dichotomous definition of severe disease, heritability was assessed in families via sib–sib correlations. Both binary indicators of severe disease and semiquantitative measures of disease severity were significantly heritable, with heritability estimates of 30% for severe disease, 37% to 39% for FECD score, and 47% for central corneal thickness. Conclusions: Genetic risk factors have a strong role in the severity of the FECD phenotype and corneal thickness. Genotyping this cohort with high-density genetic markers followed by appropriate statistical analyses should lead to novel loci for disease susceptibility.

Comparison of deep lamellar endothelial keratoplasty and penetrating keratoplasty in patients with Fuchs endothelial dystrophy.

Purpose: To evaluate and compare 1-year postoperative visual acuity, refractive results, endothelial cell density (ECD), and complications in a consecutive group of patients who underwent deep lamellar endothelial keratoplasty (DLEK) with those who underwent penetrating keratoplasty (PK) performed by 1 surgeon. Methods: We prospectively analyzed results of 20 consecutive patients with Fuchs dystrophy and pseudophakia who underwent small-incision DLEK surgery and retrospectively compared these results with those of 23 consecutive patients with Fuchs dystrophy and pseudophakia who underwent standard PK surgery during the same period. Main outcome measurements were best spectacle-corrected visual acuity (BSCVA); refractive, keratometric, and topographic astigmatism; topographic irregular astigmatism; absolute change in spherical equivalent; and ECD. Postoperative complications in the 2 groups were also analyzed. Results: Preoperative BSCVA was significantly better in the DLEK group than the PK group (P = 0.013). Postoperative BSCVA was significantly better in the DLEK group than the PK group at 6 months (P = 0.025) and similar in each group at 12 months. Twelve-month postoperative refractive, keratometric, and topographic astigmatism was significantly less in the DLEK group than the PK group (P < 0.001). Surface asymmetry index and change in keratometric spherical equivalent was significantly less in the DLEK group than the PK group at 12 months postoperatively (P < 0.001). Preoperative ECD was significantly higher in the DLEK group (3072 ± 307 cells/mm2) than the PK group (2779 ± 413 cells/mm2). Twelve-month postoperative ECD was similar in the DLEK group (1293 ± 469 cells/mm2) compared with the PK group (1303 ± 454 cells/mm2; P = 0.949, not significant). Twelve-month percent endothelial cell loss was higher than reported in previous studies but was similar in the DLEK group (57.9%) compared with the PK group (53.1%). Twelve months postoperatively, all grafts were clear in the DLEK and PK groups. Conclusions: DLEK surgery resulted in more rapid vision recovery, significantly less regular and irregular astigmatism, and less change in spherical equivalent than PK surgery. Endothelial cell loss was significant in both groups but was not significantly different in the DLEK group from the PK group. DLEK surgery has significant advantages over PK surgery, but long-term ECD and graft survival in DLEK surgery should be studied.

Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty.

Purpose: To compare the corneal and aqueous penetration and pharmacokinetics of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions and their effect on corneal reepithelialization after penetrating keratoplasty. Methods: In this randomized, open-label, parallel-controlled study, corneal and aqueous penetration and the pharmacokinetic parameters of topically applied gatifloxacin 0.3% and moxifloxacin 0.5% (2 preoperative doses of 1 drop given 5 minutes apart) were estimated by using a sparse sampling method. Corneal and aqueous samples were collected 0.25, 0.5, 1, or 2 hours after the final dose. The concentration was determined by a high-performance liquid chromatography method. Stromal Cmax:MBC50 (maximum drug concentration in serum to 50% minimum bactericidal concentration) ratios for selected ocular pathogens were also assessed. Postoperative corneal reepithelialization at days 1, 3, and 7 was evaluated and compared between groups. Results: The calculated pharmacokinetic parameters were higher with moxifloxacin 0.5% than with gatifloxacin 0.3%. The stromal Cmax was 48.5 versus 15.7 μg/g (P = 0.04), and the stromal AUC0-2 (area under the concentration-time curve from 0 to 2 hours) was 30.9 versus 13.6 μg·h/g (P < 0.05). The endothelial Cmax was 76.1 versus 7.3 μg/g (P > 0.05), and the endothelial AUC0-2 was 43.9 versus 9.8 μg·h/g (P < 0.05). The aqueous Cmax was 0.9 versus 0.3 μg/mL (P > 0.05), and the aqueous AUC0-2 was 1.2 versus 0.4 μg·h/mL (P < 0.05). Stromal Cmax:MBC50 ratios were higher in the moxifloxacin 0.5% group for each pathogen tested. The corneal reepithelialization rates were comparable between groups. Conclusions: Topical preoperative moxifloxacin 0.5% achieved greater corneal and aqueous penetration than did gatifloxacin 0.3%. The clinical significance of this difference is not known. Postoperative use of these agents had similar effects on corneal reepithelialization.

Delayed Onset and Recurrent alcaligenes xylosoxidans Keratitis

Alcaligenes xylosoxidans (formerly Achromobacter xylosoxidans) is an opportunistic aerobic gram-negative rod that is oxidase positive and nonlactose fermenting. It may be confused with other gram-negative bacteria such as Pseudomonas aeruginosa (1). The organism was first described and named in 1971 by Yabuuchi and Ohyama (2), who isolated the organism from purulent ear discharge of seven patients. It is frequently found in moist areas of hospitals and is resistant to many antimicrobial agents (3). Alcaligenes xylosoxidans is a transient colonizer of human gastrointestinal or respiratory tract in patients with cystic fibrosis (4). Its mode of transmission is often unknown, although it frequently involves exposure of debilitated patients to contaminated fluids or medical solutions (1,5,6). It has caused bacteremia, urinary tract infections, meningitis, wound infections, pneumonia, and peritonitis (6). To our knowledge, only five cases of A. xylosoxidans keratitis have been reported (Table 1). We report a case of posttraumatic A. xylosoxidans keratitis that recurred after apparent resolution.

Treatment of chronic nonhealing neurotrophic corneal epithelial defects with thymosin beta 4.

Neurotrophic keratopathy is a degenerative disease of the corneal epithelium and stroma that results from impaired corneal innervation. Reduced corneal sensitivity is responsible for producing recurring or chronic epithelial defects that may lead to subsequent ulceration and/or perforation. It is most frequently associated with topical medications, long-standing diabetes mellitus, herpes zoster ophthalmicus (HZO), herpes simplex keratitis, neurologic disease, or localized trauma. Conventional treatments include prophylactic topical antibiotic drops or ointment, frequent nonpreserved ocular lubricants, patching, and bandage contact lenses. In recalcitrant cases, oral doxycycline, autologous serum, and the surgical application of an amniotic membrane, tarsorrhaphy, or a conjunctival flap are used alone or in combination. Successful modulation healing in these patients is erratic at best and vexing for both the patient and ophthalmologist. The potent wound healing and anti-inflammatory effects of thymosin beta 4, a naturally occurring, 43–amino acid, G-actin– sequestering molecule, has been demonstrated in numerous animal and cellular models of corneal injury. We sought to evaluate thymosin beta 4 in a human disorder that did not have an infectious component or one in which stem cell dysfunction or conjunctival disruption was extensive. A preliminary unpublished evaluation of thymosin beta 4 in diabetic corneal defects was encouraging. Here we describe the treatment results of 4 patients with chronic neurotrophic corneal epithelial defects who were treated under a Food and Drug Administration investigational new drug compassionate use protocol (approved by the Wayne State University Human Investigation Committee) with a sterile, single-dose, nonpreserved, ophthalmic formulation of thymosin beta 4 eye drops supplied by RegeneRx Biopharmaceuticals, Inc (Rockville, Maryland).

The Effect of ABO Blood Incompatibility on Corneal Transplant Failure in Conditions with Low Risk of Graft Rejection

PURPOSE To determine whether corneal graft survival over a 5-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs dystrophy or pseudophakic corneal edema, conditions at low-risk for graft rejection. DESIGN Multi-center prospective, double-masked, clinical trial. METHODS ABO blood group compatibility was determined for 1,002 donors and recipients. During a 5-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were attributable to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects. RESULTS ABO donor-recipient incompatibility was not associated with graft failure attributable to any cause including graft failure because of rejection, or with the occurrence of a rejection episode. The 5-year cumulative incidence of graft failure attributable to rejection was 32 (6%) for recipients with ABO recipient-donor compatibility and 12 (4%) for those with ABO incompatibility (hazard ratio, 0.65; 95% confidence interval, 0.33 to 1.25; P = .20). The 5-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 64 (12%) for ABO compatible compared with 25 (8%) for ABO incompatible cases (P = .09). Among clear grafts at 5 years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases. CONCLUSIONS In patients undergoing penetrating keratoplasty for Fuchs dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure attributable to graft rejection.

Necrotizing Keratitis Caused by Capnocytophaga ochracea

We studied three cases of Capnocytophaga keratitis that demonstrated stromal necrosis and a ring infiltrate. In all cases, the keratitis occurred in a previously diseased or traumatized cornea. One patient was treated with chronic antiamoebic therapy for presumed Acanthamoeba keratitis. Two cases resulted in corneal perforation. Laboratory isolation was difficult because of slow, fastidious growth. Capnocytophaga is not uniformly sensitive to commonly used topical antibiotics such as the cephalosporins and aminoglycosides, but may respond to treatment with topical clindamycin.