William J. Reinhart

Descemet's Stripping Endothelial Keratoplasty: Safety and Outcomes

OBJECTIVE To review the published literature on safety and outcomes of Descemets stripping endothelial keratoplasty (DSEK) for the surgical treatment of endothelial diseases of the cornea. DESIGN Peer-reviewed literature searches were conducted in PubMed and the Cochrane Library with the most recent search in February 2009. The searches yielded 2118 citations in English-language journals. The abstracts of these articles were reviewed and 131 articles were selected for possible clinical relevance, of which 34 were determined to be relevant to the assessment objectives. RESULTS The most common complications from DSEK among reviewed reports included posterior graft dislocations (mean, 14%; range, 0%-82%), followed by endothelial graft rejection (mean, 10%; range, 0%-45%), primary graft failure (mean, 5%; range, 0%-29%), and iatrogenic glaucoma (mean, 3%; range, 0%-15%). Average endothelial cell loss as measured by specular microscopy ranged from 25% to 54%, with an average cell loss of 37% at 6 months, and from 24% to 61%, with an average cell loss of 42% at 12 months. The average best-corrected Snellen visual acuity (mean, 9 months; range, 3-21 months) ranged from 20/34 to 20/66. A review of postoperative refractive results found induced hyperopia ranging from 0.7 to 1.5 diopters (D; mean, 1.1 D), with minimal induced astigmatism ranging from -0.4 to 0.6 D and a mean refractive shift of 0.11 D. A review of graft survival found that clear grafts at 1 year ranged from 55% to 100% (mean, 94%). CONCLUSIONS The evidence reviewed is supportive of DSEK being a safe and effective treatment for endothelial diseases of the cornea. In terms of surgical risks, complication rates, graft survival (clarity), visual acuity, and endothelial cell loss, DSEK appears similar to penetrating keratoplasty (PK). It seems to be superior to PK in terms of earlier visual recovery, refractive stability, postoperative refractive outcomes, wound and suture-related complications, and intraoperative and late suprachoroidal hemorrhage risk. The most common complications of DSEK do not appear to be detrimental to the ultimate vision recovery in most cases. Long-term endothelial cell survival and the risk of late endothelial rejection are beyond the scope of this assessment. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Deep Anterior Lamellar Keratoplasty as an Alternative to Penetrating Keratoplasty: A Report by the American Academy of Ophthalmology

OBJECTIVE To review the published literature on deep anterior lamellar keratoplasty (DALK) to compare DALK with penetrating keratoplasty (PK) for the outcomes of best spectacle-corrected visual acuity (BSCVA), refractive error, immune graft rejection, and graft survival. METHODS Searches of the peer-reviewed literature were conducted in the PubMed and the Cochrane Library databases. The searches were limited to citations starting in 1997, and the most recent search was in May 2009. The searches yielded 1024 citations in English-language journals. The abstracts of these articles were reviewed, and 162 articles were selected for possible clinical relevance, of which 55 were determined to be relevant to the assessment objective. RESULTS Eleven DALK/PK comparative studies (level II and level III evidence) were identified that compared the results of DALK and PK procedures directly; they included 481 DALK eyes and 501 PK eyes. Of those studies reporting vision and refractive data, there was no significant difference in BSCVA between the 2 groups in 9 of the studies. There was no significant difference in spheroequivalent refraction in 6 of the studies, nor was there a significant difference in postoperative astigmatism in 9 of the studies, although the range of astigmatism was often large for both groups. Endothelial cell density (ECD) stabilized within 6 months after surgery in DALK eyes. Endothelial cell density values were higher in the DALK groups in all studies at study completion, and, in general, the ECD differences between DALK and PK groups were significant at all time points at 6 months or longer after surgery for all of the studies reporting data. CONCLUSIONS On the basis of level II evidence in 1 study and level III evidence in 10 studies, DALK is equivalent to PK for the outcome measure of BSCVA, particularly if the surgical technique yields minimal residual host stromal thickness. There is no advantage to DALK for refractive error outcomes. Although improved graft survival in DALK has yet to be demonstrated, postoperative data indicate that DALK is superior to PK for preservation of ECD. Endothelial immune graft rejection cannot occur after DALK, which may simplify long-term management of DALK eyes compared with PK eyes. As an extraocular procedure, DALK has important theoretic safety advantages, and it is a good option for visual rehabilitation of corneal disease in patients whose endothelium is not compromised.

Chronic Propionibacterium Endophthalmitis After Extracapsular Cataract Extraction and Intraocular Lens Implantation

We studied six cases of chronic, indolent intraocular inflammation that occurred after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The inflammation was characterized by a delayed onset, and in three cases had the clinical appearance of a granulomatous iridocyclitis. Cultures of intraocular specimens obtained from six eyes yielded Propionibacterium; five yielded P. acnes. Pleomorphic gram-positive bacilli consistent with Propionibacterium were identified in cytologic or histopathologic studies in four of the six culture-positive cases. After surgical and medical therapy, the inflammation resolved. Postoperative Propionibacterium endophthalmitis may masquerade as a chronic iridocyclitis.

Optisol Corneal Storage Medium

Optisol is an investigational, intermediate-term corneal storage medium containing chondroitin sulfate and dextran to enhance corneal dehydration during storage. We used scanning electron microscopy to grade endothelial cell morphologic characteristics in terms of cell shape, cell borders, cell swelling, and apical holes in pairs of corneas stored in Optisol and Dexsol. Optisolstored corneas showed significantly fewer morphologic changes after 14 days at 4 degrees C than did Dexsol-stored corneas. No significant differences were seen after 1 to 4 days at 26 degrees C. Temperature-reversal analysis showed no significant change in corneal thickness with warming after 2-week storage at 4 degrees C in either medium, although Optisol-stored corneas were significantly thinner than those stored in Dexsol at all times. The results of scanning electron microscopy suggest that preservation at refrigerator temperature for 2 weeks in Optisol is superior to preservation in Dexsol. Both media may be useful in preserving endothelial structure for limited periods at room temperature, which could provide a measure of safety in shipping or storage where refrigeration is unreliable.

Safety of Overnight Orthokeratology for Myopia A Report by the American Academy of Ophthalmology

OBJECTIVE To review the published literature to evaluate the safety of overnight orthokeratology (OOK) for the treatment of myopia. METHODS Repeated searches of peer-reviewed literature were conducted in PubMed (limited to the English language) and the Cochrane Central Register of Controlled Trials (no language limitations) for 2005, 2006, and 2007. The searches yielded 495 citations. The panel reviewed the abstracts of these articles and selected 79 articles of possible clinical relevance for review. Of these 79 full-text articles, 75 were determined to be relevant to the assessment objective. RESULTS No studies were rated as having level I evidence. Two premarket applications to the Food and Drug Administration were rated as having level II evidence. There were 2 studies rated as having level II evidence. The main source of reports of adverse events associated with OOK was 38 case reports or noncomparative case series (level III evidence). CONCLUSIONS The prevalence and incidence of complications associated with OOK have not been determined. Complications, including more than 100 cases of infectious keratitis resulting from gram-positive and gram-negative bacteria and Acanthamoeba, have been described in case reports and case series representing observations in undefined populations of OOK users. Data collection was nonstandard. Risk factors for various complications cannot be determined. Because OOK puts patients at risk for vision-threatening complications they may not encounter otherwise, sufficiently large well-designed cohort or randomized controlled studies are needed to provide a more reliable measure of the risks of treatment and to identify risk factors for complications. Overnight orthokeratology for slowing the progression of myopia in children also needs well-designed and properly conducted controlled trials to investigate efficacy. Because of variations in orthokeratology practice, a wide margin of safety should be built into OOK regimens. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

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.

An In Vitro and Clinical Comparison of Corneal Storage with Chondroitin Sulfate Corneal Storage Medium with and without Dextran

The safety and efficacy of 1% dextran in Chondroitin Sulfate Corneal Storage Medium (CSM) in reducing corneal swelling after 4 degrees C storage was assessed in a corneal endothelial cell culture system. No difference was found in 3H-thymidine incorporation by cells incubated in either CSM-dextran medium or CSM medium alone. Subsequently, 21 pairs of corneas, stored in either CSM or CSM-dextran from 30 to 112 hours, were transplanted into 42 eyes of 42 patients, paired by diagnostic group and procedure. All CSM grafts and 19 of 21 CSM-dextran grafts were clear at 4 months with no primary donor failures in either group. Intraoperative corneal thickness was significantly greater in the CSM group (0.82 +/- 0.07 mm) than the CSM-dextran group (0.76 +/- 0.06 mm); however, the two groups did not differ thereafter. No differences in all endothelial morphometric parameters were noted between the two groups pre- and postoperatively. Average endothelial cell loss by 4 months was 13.0 +/- 16.4% for the CSM group and 16.4 +/- 15.5% for the CSM-dextran group. The addition of dextran to CSM medium results in significant intraoperative corneal thinning without adversely affecting endothelial DNA synthesis in vitro and endothelial survival in vivo.

Indomethacin as a means of preventing cystoid macular edema following, intracapsular cataract extraction

It has been theorized that prostaglandins E1 and E2 may be responsible for the vascular leakage leading to cystoid macular edema following cataract extraction. Indomethacin is a known inhibitor of prostaglandin synthesis. A prospective, double-blind study to evaluate the effect of oral indomethacin on four and eight week cases of postoperative CME following intracapsular cataract extraction as determined by fluorescein angiography was carried out on 42 patients. Twenty patients received 25 mg of indomethacin three times a day for three days preoperatively and three weeks postoperatively. Twenty-two patients received a placebo on an identical schedule. Four (20%) patients in the indomethacin group and five (22.7%) patients in the placebo group had positive angiograms for CME. No contributory factor resulting in CME was found.

An unusual case of fungal keratitis: Metarrhizium anisopliae.

Purpose. To report a case of fungal keratitis caused by Metarrhizium anisopliae, which to our knowledge is the first reported case in the United States. Method. Case report. Results. A 36-year-old female librarian who wore extended-wear soft contact lenses was seen by an ophthalmologist on September 11 for an irritated right eye, and a corneal ulcer was diagnosed. Symptoms increased by September 27, and the patient was referred to another ophthalmologist who cultured the ulcer and had scrapings examined, which were Gram-negative for microorganisms. The patient was referred to one of the authors (W.J.R.). Her exam on October 1 showed vision corrected to 20/25 OD, a 5-mm epithelial defect with a 2.5-mm anterior stromal grayish-type infiltrate, and a quiet anterior chamber; the eye did not appear to be inflamed. The patient was reexamined on October 4 and was noted to have worsening vision. Because the initial cultures remained negative, the patient underwent a corneal biopsy, Gram stain, and cultures on October 6. Scrapings at the time of the biopsy revealed septate hyphal elements, as did the biopsy specimen, and on October 7, the patient was started on a treatment of bacitracin ointment once a day and natamycin 5% every hour. The eye gradually quieted down. A mold growing from the biopsy culture, which had been sent to a reference laboratory in San Antonio, Texas, was identified as M. anisopliae var. anisopliae. The patient was subsequently fitted with a rigid gas permeable lens, which resulted in a best-corrected visual acuity of 20/20, although glare remained a major problem. Conclusion. Although not previously reported in the United States, M. anisopliae can cause a keratomycosis, and one must consider this common insect pathogen in the differential diagnosis of fungal keratitis.

Late-stage progressive corneal astigmatism after penetrating keratoplasty for keratoconus

Purpose: Progressive corneal astigmatism occurring at least 10 years after penetrating keratoplasty for keratoconus is a late-phase complication of surgery. This report characterizes this condition in a series of patients from three corneal referral centers in the United States. Methods: Charts were retrospectively reviewed which met the following criteria: penetrating keratoplasty performed for keratoconus at least 10 years ago, keratometry or simulated keratometry from topography as well as manifest refraction recorded at least 6 months after the last suture removal (“baseline”), and an increase in corneal astigmatism of at least three D over baseline recorded at least 5 years later. Patients who had any other corneal or intraocular surgery performed were excluded. Results: Data from 15 patients (11 males and 4 females) who had penetrating keratoplasties performed by 8 different surgeons are included in this descriptive series. Postoperative follow-up averaged 17.27 years (range 11–24 years). The average donor button size was 7.83 mm (range 7.25–8.5 mm). Baseline corneal astigmatism was obtained an average of 5.2 years after penetrating keratoplasty (range 1.5–16 years) and was on average 3.57 ± 1.8 D (10 with-the-rule [WTR], 3 against-the-rule [ATR], 2 oblique). Corneal astigmatism significantly increased to an average of 11.23 ± 3.56 D (range 8.00–19.37 D, P < 0.0001) and most astigmatism was regular and WTR (9 WTR, 3 ATR, 3 oblique) 15.3 years (range 10–22 years) after surgery. Inferior steepening on topography was often noted, even those with oblique and ATR axes. Conclusions: High, late-stage, regular astigmatism after penetrating keratoplasty for keratoconus is described in a series of patients occurring at least 10 years after surgery. Possible mechanisms of this progressive astigmatism are recurrence of keratoconus in the graft, progressive corneal thinning of the host cornea, or progressive misalignment of the graft–host interface over time.