George O. D. Rosenwasser

Comparison of Ciprofloxacin Ophthalmic Solution 0.3% to Fortified Tobramycin-Cefazolin in Treating Bacterial Corneal Ulcers

PURPOSE The purpose of the study is to compare the clinical efficacy and safety of ciprofloxacin ophthalmic solution 0.3% (Ciloxan) with a standard therapy regimen (fortified tobramycin, 1.3%-cefazolin, 5.0%) for treating bacterial corneal ulcers. METHODS This randomized, parallel group, double-masked, multicenter study was conducted in 324 patients at 28 centers in the United States, Europe, and India. Patients were randomized into 2 treatment groups: 160 to ciprofloxacin and 164 to fortified tobramycin-cefazolin. Positive microbiologic cultures were obtained in 188 (58%) of 324 patients. Of these, 176 patients met protocol criteria and were evaluated for treatment efficacy: 82 in the ciprofloxacin group and 94 in the standard therapy group. The dosing schedule for both treatment groups was 1 to 2 drops of the first study medication (ciprofloxacin or fortified tobramycin) every 30 minutes for 6 hours, then hourly for the remainder of day 1; 1 to 2 drops every hour on days 2 and 3; 1 to 2 drops every 2 hours on days 4 and 5, followed by 1 to 2 drops every 4 hours on days 6 to 14. The second medication (ciprofloxacin or cefazolin) was instilled 5 to 15 minutes after the first drug, following the same dosing frequency. Physicians judgment of clinical success, cure rate, changes in ocular sings, and symptoms and the rate of treatment failures were the primary efficacy criteria. RESULTS Topical ciprofloxacin monotherapy is equivalent clinically and statistically to the standard therapy regimen of fortified antibiotics. No statistically significant treatment differences were found between ciprofloxacin (91.5%) and standard therapy (86.2%) in terms of overall clinical efficacy (P = 0.34). Similarly, no differences were noted in resolution of the clinical signs and symptoms (P > 0.08) or the time to cure (P = 0.55). The incidence of treatment failures was less in the ciprofloxacin group (8.5%) compared with the standard therapy group (13.8%). Significantly fewer patients treated with ciprofloxacin reported discomfort than did patients treated with the standard therapy regimen (P = 0.01). CONCLUSION Ciprofloxacin ophthalmic solution 0.3% monotherapy is equivalent clinically and statistically to standard therapy (fortified tobramycin-cefazolin) for the treatment of bacterial corneal ulcers and produces significantly less discomfort.

Bacterial keratitis following laser in situ keratomileusis

Abstract Purpose The development of bacterial keratitis after laser in situ keratomileusis (LASIK) has been described in only a few isolated cases. We report the development of bacterial keratitis as a postoperative complication of LASIK in three subjects. Design A retrospective interventional small case series. Participants Three patients who underwent LASIK for correction of myopia during July and August 1998 and had bacterial keratitis develop after surgery. Methods Bacterial keratitis was encountered in the operated eyes between 1 and 22 days after surgery. Topical antibiotic therapy was administered. In one eye, which had significant opacification and irregularity of the flap was developed, lamellar keratoplasty was performed. Main outcome measures Postoperative inflammation was followed clinically and photographically until it resolved. Visual acuity was measured at intervals throughout the follow-up period. Results Keratitis resolved within 3 to 16 days of starting antibiotic therapy. The final best-corrected visual acuities were 20/30, 20/15, and 20/25. Conclusions Although infectious keratitis after LASIK is an infrequently reported event, it should be discussed preoperatively with patients as a possible complication.

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.

Ocular rosacea in blacks.

In three black men (57, 64, and 61 years old) with the ocular manifestations of rosacea, the diagnosis was not initially suspected because the pathognomonic skin changes of rosacea were obscured by the skin hyperpigmentation. Ocular involvement ranged from blepharitis and conjunctival hyperemia to sight-threatening problems such as corneal neovascularization, thinning, ulceration, and perforation. Treatment with oral tetracycline and topical corticosteroids appeared to be as effective in these patients as in previously described white patients.

Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy

The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 × 10−8): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114. We also observe an overwhelming effect of the established TCF4 locus. Interestingly, we detect differential sex-specific association at LAMC1, with greater risk in women, and TCF4, with greater risk in men. Combining GWAS results with biological evidence we expand the knowledge of common FECD loci from one to four, and provide a deeper understanding of the underlying pathogenic basis of FECD.

Cornea preservation time study: methods and potential impact on the cornea donor pool in the United States.

Purpose: The aim of this study was to describe the aims, methods, donor and recipient cohort characteristics, and potential impact of the Cornea Preservation Time Study (CPTS). Methods: The CPTS is a randomized clinical trial conducted at 40 clinical sites (70 surgeons) designed to assess the effect of donor cornea preservation time (PT) on graft survival 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK). Eyes undergoing surgery for Fuchs endothelial corneal dystrophy or pseudophakic/aphakic corneal edema were randomized to receive donor corneas stored ⩽7 days or 8 to 14 days. Donor and patient characteristics, tissue preparation and surgical parameters, recipient and donor corneal stroma clarity, central corneal thickness, intraocular pressure, complications, and a reading center-determined central endothelial cell density were collected. Surveys were conducted to evaluate pre-CPTS PT practices. Results: The 1330 CPTS donors were: 49% >60 years old, 27% diabetic, had a median eye bank–determined screening endothelial cell density of 2688 cells/mm2, and 74% eye bank prepared for DSAEK. A total of 1090 recipients (1330 eyes including 240 bilateral cases) had: median age of 70 years, were 60% female, 90% white, 18% diabetic, 52% phakic, and 94% had Fuchs endothelial corneal dystrophy. Before the CPTS, 19 eye banks provided PT data on 20,852 corneas domestically placed for DSAEK in 2010 to 2011; 96% were preserved ⩽7 days. Of 305 American Academy of Ophthalmology members responding to a pre-CPTS survey, 233 (76%) set their maximum PT preference at 8 days or less. Conclusions: The CPTS will increase understanding of factors related to DSAEK success and, if noninferiority of longer PT is shown, will have great potential to extend the available pool of endothelial keratoplasty donors. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01537393.

Dislocation of the Donor Graft to the Posterior Segment in Descemet Stripping Automated Endothelial Keratoplasty

PURPOSE To report a series of dislocations of the donor graft into the posterior segment associated with Descemet stripping endothelial keratoplasty (DSAEK) and to identify possible risk factors for dislocation and clinical outcomes. DESIGN Retrospective case series. METHODS Cases of donor graft dislocation into the posterior segment associated with endothelial keratoplasty were identified from the clinical experience of 7 surgeons. Observations included the preoperative surgical history of each eye, preoperative and postoperative visual acuity, management of the complication, and the postoperative clinical course. No identified cases were excluded from this series. RESULTS Eight posterior graft dislocations were associated with DSAEK surgery. Each eye had a history of vitrectomy. Five eyes had sutured posterior chamber intraocular lenses, 1 eye had a sulcus intraocular lens, and 2 eyes were aphakic. Each eye required repeat grafting, and in 6 of 8 eyes, pars plana vitrectomy was used to remove the dislocated graft. Final visual acuities ranged from 20/30 to no light perception. CONCLUSIONS Graft dislocation into the posterior segment is a rare complication of DSAEK surgery that can lead to permanent vision loss. It has occurred in eyes that have undergone previous vitrectomy and complicated intraocular lens placement or were aphakic. As is the case with a dropped lens nucleus during cataract extraction, visual acuities after a dropped DSAEK graft range from very good to no light perception. Better postoperative results seem to be associated with prompt removal of the posteriorly dislocated graft.

Posterior Amorphous Corneal Dystrophy Is Associated with a Deletion of Small Leucine-rich Proteoglycans on Chromosome 12

Posterior amorphous corneal dystrophy (PACD) is a rare, autosomal dominant disorder affecting the cornea and iris. Next-generation sequencing of the previously identified PACD linkage interval on chromosome 12q21.33 failed to yield a pathogenic mutation. However, array-based copy number analysis and qPCR were used to detect a hemizygous deletion in the PACD linkage interval containing 4 genes encoding small leucine-rich proteoglycans (SLRPs): KERA, LUM, DCN, and EPYC. Two other unrelated families with PACD also demonstrated deletion of these SLRPs, which play important roles in collagen fibrillogenesis and matrix assembly. Given that these genes are essential to the maintenance of corneal clarity and the observation that knockout murine models display corneal phenotypic similarities to PACD, we provide convincing evidence that PACD is associated with haploinsufficiency of these SLRPs.

Textural interface opacity after descemet stripping automated endothelial keratoplasty: a report of 30 cases and possible etiology.

Purpose: Descemet stripping automated endothelial keratoplasty (DSAEK) has its own set of complications including interface abnormalities. This case series presents the largest number of patients who developed textural interface opacity (TIO) at the graft–host interface after DSAEK. Methods: This is a retrospective multicenter case series of 30 patients from 7 institutions with the finding of TIO. Clinical information collected included donor preparation details, recipient information, and surgical technique. Clinical outcomes included best-corrected visual acuity and status of TIO appearance at the last follow-up visit. Slit-lamp photographs were analyzed and compared. Results: The majority of the patients (73%) had a best-corrected visual acuity of 20/40 or better. Four of the donor tissues were prepared with a microkeratome blade with the same lot number. Six patients had a central interface space between host and donor stromal surfaces—presumed interface fluid but potentially viscoelastic. A slight majority (57%) of patients had improvement in the severity of TIO, with 20% noted to have a complete resolution of TIO (mean follow-up of 11.9 months). Two clinical types of TIO were seen: an elongated type and a punctate type. Conclusions: Most patients with TIO after DSAEK obtain good visual outcomes. TIO spontaneously improves or even resolves during follow-up without intervention. The etiology of this condition is unknown, but we propose 2 different mechanisms. The elongated type could be secondary to an irregular cut of the donor with the microkeratome blade. The punctate type may be secondary to retained viscoelastic.

Linkage of Posterior Amorphous Corneal Dystrophy to Chromosome 12q21.33 and Exclusion of Coding Region Mutations in KERA, LUM, DCN, and EPYC

PURPOSE To identify the genetic basis of posterior amorphous corneal dystrophy (PACD) segregating in a large pedigree. METHODS The authors performed clinical evaluation of a previously unreported pedigree with PACD, light and electron microscopic examination of an excised corneal button, genomewide linkage analysis, fine mapping linkage and haplotype analysis, and screening of four candidate genes (KERA, LUM, DCN, and EPYC). RESULTS Twenty-one participants were determined to be affected based on the presence of characteristic clinical features of PACD; 15 affected and 39 unaffected individuals from a single pedigree enrolled in the study and provided DNA for analysis. Histopathologic examination of an excised corneal specimen from an affected individual demonstrated disorganized stromal lamellae and stromal staining with colloidal iron. Genomewide analysis demonstrated significant evidence of linkage to chromosome region 12q21.33 and evidence suggestive of linkage to chromosome region 8q22.3. Fine mapping of the chromosome 12 locus confirmed significant linkage; the largest multipoint log odds ratio score was 5.6 at D12S351. The linkage support interval was approximately 3.5 Mb (3.5 cM) in length between flanking markers D12S1812 and D12S95, roughly the entire chromosome band 12q21.33. No coding region mutations were identified in four candidate genes-KERA, LUM, DCN, EPYC-located in the chromosome 12 linkage support interval. CONCLUSIONS Linkage and haplotype analyses identified 12q21.33 as a locus for PACD. However, no mutations were identified in the candidate genes (KERA, LUM, DCN, EPYC) within this region.