Stephen C. Kaufman

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.

Corneal thickness measurements with the Orbscan Topography System and ultrasonic pachymetry

Purpose: To compare corneal thickness measurements obtained with a new instrument, the Orbscan Topography System, with those obtained with the DGH ultrasonic pachymeter and to assess the agreement and repeatability of the two devices. Setting: LSU Eye Center, New Orleans, Louisiana, USA. Methods: Measurement agreement was assessed in 51 eyes of 26 normal volunteers using both Orbscan and ultrasonic pachymetry. Repeatability for the instruments was measured in 10 eyes of 5 additional volunteers. Corneal thicknesses were compared using the analysis of variance (ANOVA). The relationship between the devices was assessed by analysis of regression (ANOR). Results: In the measurement agreement experiment, the mean corneal thickness was 571.3 &mgr;m ± 6.21 SEM with the Orbscan system and 543.3 ± 7.49 &mgr;m with ultrasonic pachymetry; these values were significantly different (F test, ANOVA, P = .0048). In the repeatability experiment, the mean thickness was 561.1 ± 8.42 &mgr;m with the Orbscan system and 537.4 ± 5.84 &mgr;m with ultrasound pachymetry; these values were also significantly different (F test, ANOVA, P = .0003). Analysis of regression showed a significant linear regression between the values obtained with the devices (P = .0001, F test, ANOR). Conclusions: In both studies, the Orbscan system obtained statistically significantly different and higher values for corneal thickness. Regression analysis suggests that over the range of values in this study, the two devices differ by a constant amount (intercept and slope). The nonzero intercept of this regression shows that the values from the devices differ and cannot be directly substituted for each other. We therefore conclude that in this study, Orbscan system measurements of corneal thickness were 23 to 28 &mgr;m greater than ultrasonic pachymeter measurements. Linear regression equations may be developed for the results of measurements from the two devices and used as a precise transformation factor for the values obtained with the two devices.

Interface inflammation after laser in situ keratomileusis: Sands of the Sahara syndrome

Purpose: To determine the source of the interface debris that causes the interface inflammation known as “sands of the Sahara” after laser in situ keratomileusis (LASIK). Setting: Department of Ophthalmology, LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans, USA. Methods: A microkeratome (Automated Corneal Shaper) was used to make a LASIK flap in 8 eyes of 4 rabbits. In 4 eyes, the blade was used directly from the sterile pack; in the contralateral 4 eyes, the blade was cleaned prior to use. In vivo confocal microscopy of the corneas was performed 1 day after surgery. An unused, cleaned blade and an unused, uncleaned blade, as well as blades used in the rabbit eyes, were examined by scanning electron microscopy. Methods: Confocal microscopy revealed numerous fragments of debris surrounded by inflammatory cells in the LASIK flap interfaces created by blades taken directly from the sterile package. Interfaces created by the cleaned blades showed only rare, scattered bits of debris. Scanning electron microscopy of the unused blades showed debris on the uncleaned blade removed directly from the sterile package. Conclusion: Post‐LASIK interface inflammation may be caused by debris on the microkeratome blade, although other sources are possible. The interface debris and inflammation can be reduced or eliminated by cleaning the microkeratome blade before use.

Options and Adjuvants in Surgery for Pterygium: A Report by the American Academy of Ophthalmology

OBJECTIVE To assess the outcomes and safety of current surgical options and adjuvants in the treatment of primary and recurrent pterygium. METHODS Literature searches of the PubMed and the Cochrane Library databases were last conducted in January 2011 using keywords and were restricted to randomized controlled trials reporting on surgical intervention for pterygium. The searches were limited to articles published in English and yielded 120 citations. Citation abstracts, and if necessary the full text, were reviewed to identify randomized controlled trials that reported recurrence as an outcome measure and had a mean follow-up of at least 6 months. Fifty-one studies comparing bare sclera excision, conjunctival or limbal autograft, intraoperative mitomycin C, postoperative mitomycin C, and amniotic membrane transplantation for primary and recurrent pterygia fit these inclusion criteria. RESULTS Four studies demonstrated that the conjunctival or limbal autograft procedure is more efficacious than amniotic membrane placement. Use of conjunctival or limbal autografts or mitomycin C during or after pterygium excision reduced recurrence compared with bare sclera excision alone in most studies of primary or recurrent pterygium. The outcomes of conjunctival or limbal autograft were similar to outcomes for intraoperative mitomycin C in the few studies that directly compared the 2 techniques. There is evidence that increased concentration and duration of exposure to intraoperative mitomycin C is associated with increased efficacy. Of the adjuvants studied, only mitomycin C was associated with vision-threatening complications, including scleral thinning, ulceration, and delayed conjunctival epithelialization; there is some evidence of increasing complications with increased concentration and duration of exposure. There is conflicting evidence as to whether increasing age is protective against recurrence, but the morphologic features of the pterygium were shown to affect the recurrence rate. CONCLUSIONS Evidence indicates that bare sclera excision of pterygium results in a significantly higher recurrence rate than excision accompanied by use of certain adjuvants. Conjunctival or limbal autograft was superior to amniotic membrane graft surgery in reducing the rate of pterygium recurrence. Among other adjuvants, there is evidence that mitomycin C and conjunctival or limbal autografts reduce the recurrence rate after surgical excision of a pterygium. Furthermore, the data indicate that using a combination of conjunctival or limbal autograft with mitomycin C further reduces the recurrence rate after pterygium excision compared with conjunctival or limbal autograft or mitomycin C alone. Additional studies are necessary to determine the long-term effects, optimal route of administration, and dose and duration of treatment for mitomycin C. Factors such as availability of resources, primary or recurrent status of pterygium, age of patient, and surgeon or patient preference may influence the surgeons choice of adjuvant because there are insufficient data to recommend a specific adjuvant as superior. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Confocal microscopy in cornea guttata and Fuchs' endothelial dystrophy

AIMS To report the appearances of cornea guttata and Fuchs’ endothelial dystrophy from white light confocal microscopy. METHODS Seven eyes of four consecutive patients with cornea guttata were prospectively examined. Of the seven eyes, three also had corneal oedema (Fuchs’ dystrophy). In vivo white light tandem scanning confocal microscopy was performed in all eyes. Results were compared with non-contact specular microscopy. RESULTS Specular microscopy was precluded by corneal oedema in one eye. In the remaining six eyes, it demonstrated typical changes including pleomorphism, polymegathism, and the presence of guttae appearing as dark bodies, some with a central bright reflex. In all seven eyes, confocal microscopy revealed the presence of round hyporeflective images with an occasional central highlight at the level of the endothelium. Changes in cell morphology and size were readily appreciated. CONCLUSION By comparison with specular microscopy, the hyporeflective images with an occasional central highlight seen on confocal microscopy are consistent with the presence of guttae. Confocal microscopy may confirm the diagnosis of cornea guttata and Fuchs’ endothelial dystrophy by demonstrating the presence of guttae. This technique is especially valuable in cases of corneal oedema, where specular microscopy may fail to visualise the endothelium. However, specular microscopy should remain the method of choice to evaluate the endothelium, principally because it is easier to use.

K-Sol corneal preservation.

K-Sol, a new cornea preserving solution which contains no calf serum of foreign protein and is used for refrigerated storage of donor tissue, has storage procedures identical to those currently used for tissue preservation in McCarey-Kaufman medium. K-Sol can keep corneas alive and usable for penetrating keratoplasty for at least two weeks. The clinical results in a series of 17 patients indicated that tissue preserved in K-Sol for as long as two weeks, even when used by inexperienced surgeons in difficult or unfavorable cases requiring extensive anterior segment reconstruction, including reoperations or retained intraocular lenses, gave results virtually identical to those obtained with tissue preserved in McCarey-Kaufman medium for only two or three days.

Corneal collagen cross-linking: a confocal, electron, and light microscopy study of eye bank corneas.

Purpose: The purpose of this study was to evaluate morphological changes induced by corneal collagen cross-linking in a human ex vivo cornea, using confocal, electron, and light microscopy. Methods: The central epithelium was partially removed from ex vivo human corneal buttons. Riboflavin 0.1% solution was applied before ultraviolet A light treatment and then for every 2 minutes for 30 minutes while the corneas were exposed to ultraviolet A light at a wavelength of 370 nm and intensity of 3 mW/cm2. Each cornea was evaluated using confocal, electron, and light microscopy. Results: Confocal microscopy demonstrated normal-appearing corneas on their initial pretreatment examination, with reduced stromal detail. After treatment, a superficial layer of highly reflective spherical structures (4-10 μm) was observed. Many of these hyperreflective structures appeared up to a depth of 300 μm. The remainder of the corneal stroma and endothelium appeared normal. Electron microscopy showed keratocyte apoptotic changes to a depth of 300 μm. No observable pathologic changes were seen on histology. Conclusions: Based on clinical studies, corneal cross-linking is a promising treatment that appears to be safe and to halt ectatic corneal disease progression. Initial European studies used animal models to extrapolate human protocols. In conjunction with clinical studies, we believe that human ex vivo corneal studies provide a means to evaluate the structural and morphological changes associated with this procedure, within human corneas, in a manner that cannot be accomplished in vivo.

How has confocal microscopy helped us in refractive surgery

Purpose of review To summarize the known uses of in-vivo confocal microscopy in refractive surgery, highlighting the current developments in the field. Recent findings Examination of the cornea after laser in-situ keratomileusis demonstrated that the keratocyte density within the laser in-situ keratomileusis flap and anterior residual corneal bed continued to decline during the entire 3-year period of the study. The progressive loss of keratocytes in the flap and anterior portion of the residual corneal bed could have long-term implications in terms of corneal stability, refractive stability and cellular integrity after laser in-situ keratomileusis. Additional studies showed that the density of sub-basal nerves decreased by 90% 1 month after laser in-situ keratomileusis. At some point between 3 and 6 months after laser in-situ keratomileusis, the sub-basal nerves began to recover and by 2 years they had reached approximately 50% of their original preoperative density. Analysis of sub-basal nerve density after photorefractive keratectomy reported that the nerve density completely recovered to preoperative levels by 2 years. Other confocal microscopic studies demonstrated that the microscope can detect infectious organisms in vivo, without stains or dyes. Summary The confocal microscope is a unique diagnostic instrument that can be used to evaluate corneal healing, long-term stability and to assess complications after refractive surgery. The ability of the device to view in-vivo cellular detail, microorganisms, inflammatory cells, epitheliod cells, fibrosis and measure the postoperative thickness of the residual corneal bed after laser in-situ keratomileusis, in a noninvasive manner, highlights the unique capabilities of this instrument.

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.