Elisabeth Pels

Histopathologic Effects of Mitomycin C After Trabeculectomy in Human Glaucomatous Eyes With Persistent Hypotony

We evaluated the histopathologic findings in seven patients who underwent surgical revision of the filtration site after trabeculectomy with mitomycin C because of persistent hypotonous maculopathy. Light microscopic examination of subconjunctival tissue and sclera demonstrated hypocellularity of fibroblasts and disruption of the normal architecture. Tissue fragments at the margin of the bleb wall demonstrated scarring and contained multiple fibroblasts. Additionally, we investigated the histopathologic changes in an eye obtained from a patient who died one week after a trabeculectomy with mitomycin C. Transmission electron microscopy showed myelin figures, increased melanolipofuscin granules, vacuolated cytoplasm, and disrupted mitochondria of the ciliary body epithelium underlying the site of mitomycin C application. On the basis of these findings, both overfiltration because of tissue disorganization of the filtering bleb and aqueous hyposecretion because of ciliary body toxicity might be involved in the causes of persistent hypotony after mitomycin C trabeculectomy.

Endothelial cell loss and visual outcome of deep anterior lamellar keratoplasty versus penetrating keratoplasty: a randomized multicenter clinical trial

OBJECTIVE To compare endothelial cell (EC) loss, visual and refractive outcomes, and complications after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK). DESIGN Randomized, multicenter clinical trial. PARTICIPANTS Fifty-six eyes of 56 patients with a corneal stromal pathology not affecting the endothelium were randomized to DALK or PK. METHODS The DALK procedure was performed according to Anwars big-bubble technique. Patients underwent an ophthalmic examination preoperatively and 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES Endothelial cell loss, refractive and topographic astigmatism, spherical equivalent, uncorrected visual acuity, and best spectacle-corrected visual acuity (BSCVA) were measured, and complications were recorded. RESULTS Endothelial cell loss was significantly higher after PK compared with DALK procedures performed without perforation of Descemets membrane (12 months: 27.7% ± 11.1% vs. 12.9% ± 17.6%). The BSCVA was significantly better in the PK group at 3 and 6 months after surgery but was not significantly different 12 months after surgery (0.39 ± 0.3 logarithm of the minimum angle of resolution [logMAR] in DALK and 0.31 ± 0.3 logMAR in PK). At 12 months postoperatively, refractive and topographic astigmatism in the DALK and PK groups were -3.37 ± 2.3 diopters (D) and -3.76 ± 2.1 D (P = 0.53), and 3.57 ± 2.3 D and 4.16 ± 2.0 D (P = 0.34), respectively. (Micro)perforation of the Descemets membrane occurred in 32% (9/28) of the DALK eyes, and 18% (5/28) of the patients required conversion to PK. Endothelial cell loss was not significantly different between DALK and PK when cases with perforation of Descemets membrane were included in the (intention-to-treat) analysis (12 months: 19.1 ± 21.6 vs. 27.7 ± 11.1 P = 0.112). Rejection episodes were reported in 1 patient in the DALK group (epithelial rejection) and 3 patients in the PK group (all endothelial rejections). No graft failure occurred. CONCLUSIONS One year after DALK performed without perforation of Descemets membrane, EC loss is significantly lower, whereas the BSCVA is comparable to that in the PK group. In addition, no endothelial rejection occurred in the DALK group. However, Descemets membrane perforation remains a major complication in DALK and warrants improvements to standardize the big-bubble technique.

Efficacy and safety of femtosecond laser-assisted corneal endothelial keratoplasty: a randomized multicenter clinical trial.

Background. To evaluate the efficacy and safety of femtosecond laser-assisted endothelial keratoplasty (FLEK) versus penetrating keratoplasty (PK) in patients with corneal endothelial disease. Methods. A randomized multicenter clinical trial of 80 eyes of 80 patients with corneal endothelial disease were randomized to FLEK or PK. Clinical outcomes (astigmatism and visual acuity) and incidence of postoperative complications were compared between the two groups. Results. At 12 months, the percentage of eyes with a refractive astigmatism less than or equal to 3 diopters was higher in the FLEK group in comparison with the PK group (86.2% vs. 51.3%, P=0.004). The mean postoperative best corrected visual acuity was 20/70±2 lines in the FLEK group and 20/44±2 lines in the PK group (P<0.001), but the gain in the best corrected visual acuity between the two groups was not significantly different. The endothelial cell loss in the FLEK and PK group was 65±12% and 23±15% (P<0.001). The most common postoperative complication in the FLEK group was graft dislocation (27.8%). Wound healing related problems occurred in six eyes (15%) in the PK group and in none of the FLEK eyes. Conclusions. FLEK effectively reduces postoperative astigmatism and results in an absence of wound healing related problems in patients with endothelial disease. However, visual acuity is lower as compared with conventional PK, and the high level of endothelial cell loss warrants a modification of the insertion technique of the endothelial graft.

Preliminary results of femtosecond laser-assisted descemet stripping endothelial keratoplasty

OBJECTIVE To evaluate the preliminary visual results of femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS-DSEK). METHODS We prospectively analyzed results of 20 consecutive patients with Fuchs endothelial dystrophy or aphakic/pseudophakic bullous keratopathy who underwent FS-DSEK. Best spectacle-corrected visual acuity (BSCVA), refraction, corneal topography, and endothelial cell density were measured preoperatively and 3 and 6 months after FS-DSEK. Corneal thickness was measured using an optical coherence tomography technique. RESULTS The average BSCVA of 11 eyes with normal visual potential significantly improved from 20/110 +/- 4 lines to 20/57 +/- 1 line at 6 months (P < .007). At 6 months, the mean (SD) hyperopic shift was 2.24 (2.3) diopters (D). Preoperative and 6 months postoperative refractive astigmatism were -0.75 (0.9) D and -1.58 (1.1) D (P = .01), but the topographic astigmatism did not change postoperatively (P = .95). Mean (SD) endothelial cell density at 6 months was 1368 (425) cells/mm(2). There was a persistent deswelling of the graft up to 3 months postoperatively. Complications included graft dislocations requiring repositioning (20%), pupillary block glaucoma (5%), epithelial ingrowth (5%), and primary graft failure (5%). CONCLUSIONS Femtosecond laser-assisted Descemet stripping endothelial keratoplasty was effective in treating endothelial failure with minimal induced refractive astigmatism, limited improvement of BSCVA, and induction of a hyperopic shift. Endothelial cell count and dislocation rate were significant, which may be related to the surgical technique.

Femtosecond laser-assisted inverted mushroom keratoplasty.

PURPOSE To evaluate best-corrected visual acuity (BCVA), refractive outcome, corneal topography, optical coherence tomography, and endothelial cell density 12 months after femtosecond laser-assisted inverted mushroom keratoplasty. METHODS We performed a prospective study of a surgical case series of 5 patients undergoing femtosecond laser-assisted inverted mushroom keratoplasty for pseudophakic bullous keratopathy or pre-Descemet X-linked ichthyosis. The femtosecond laser was used to create a top-hat configuration in the donor cornea and recipient cornea. Laser parameters were as follows: energy, 4.0 (anterior inner vertical side cut and horizontal lamellar cut) and 7.0 microJ (posterior outer vertical side cut); spiral pattern with a firing rate of 15 kHz. The size of the anterior inner diameter was 7.4 mm in the donor cornea and 7.0 mm in the recipient cornea. The posterior outer diameter was 9.0 mm in all eyes. RESULTS At 6 and 12 months after surgery, all corneal grafts were clear and showed an excellent adaptation of the lamellar donor and recipient wound surfaces. At 12 months postoperatively, BCVA averaged 20/32 (range, 20/60-20/20), refractive cylinder averaged -3.20 +/- 2.0 D, topographical cylinder averaged 3.26 +/- 2.1 D, and the mean endothelial cell density was 1793 +/- 491 cells/mm2 (range, 954-2237 cells/mm2). The mean central corneal thickness and thickness of the posterior shelf was 517 +/- 3 and 175 +/- 8 microm, respectively. CONCLUSIONS The femtosecond laser-assisted inverted mushroom keratoplasty shows good promise in surgical treatment of corneal diseases. The multiplanar fit between the donor and recipient cornea allows early suture removal and visual rehabilitation.

The effects of organ-culture on the density of keratocytes and collagen fibers in human corneas.

Purpose. Keratocytes are important in regaining corneal transparency during wound healing after surgery or trauma. Hitherto, there are still controversies concerning the effects of organ culture on the density and integrity of keratocytes and collagen fibers. The current study aimed at a systematic analysis of the effects of organ-culture on the morphology and density of keratocytes and collagen fibers. Methods. Human corneas were organ-cultured in MEM for 7 (n=17, 3 pairs), 14 (n=18, 9 pairs) and 21days (n=18, 9 pairs). Of the pairs one cornea was processed in swollen condition and the fellow cornea after reversal of swelling in MEM plus Dextran. Eleven post-mortem corneas (PM) and 11 fresh corneas obtained from melanoma patients were used as controls. Stromal thickness, number of keratocyte profiles (corrected for swelling), number and diameter of collagen fibers were measured in light microscopical sections and electron micrographs. Results. Stromal swelling due to organ-culture resulted in large keratocyte profiles with many vacuoles and large distances between collagen fibers in the posterior stroma. In contrast both keratocytes and distances between collagen fibers were not affected in the anterior stroma. After reversed-swelling the posterior corneal stroma was similar to that in fresh controls, indicating that the swelling process is largely reversible. The initial decrease in keratocyte density (18%) in the early post-mortem period did not progress during 21 days of organ culture. Conclusion. With respect to the morphology and density of keratocytes and collagen fibers it can be concluded that donor corneas remain suitable for transplantation up to at least 21days after organ-culture.

Histologic evaluation of human posterior lamellar discs for femtosecond laser Descemet's stripping endothelial keratoplasty.

Purpose: To evaluate the histologic changes in corneal structure after femtosecond laser preparation of posterior lamellar discs, more specifically, the smoothness of the stromal bed and the accuracy of the predicted depth of the horizontal lamellar cut. Materials and methods: Nineteen human donor eyes unsuitable for transplantation were used. Femtosecond laser was used to prepare a horizontal lamellar cut in donor corneas at a depth of 400 μm. Transmission electron microscopy images were used to evaluate the changes in the corneal structure and to measure the damage zone. Scanning electron microscopy images were used to determine the relative depth of the horizontal lamellar cut, and the stromal bed was examined to determine the smoothness of the surface. Results: Transmission electron microscopy images showed a mean damage zone of 6.8 ± 3.1 μm, which consisted of irregularly oriented collagen fibrils and electron-dense granular material. The collagen lamellae, both anteriorly and posteriorly of the damaged zone, showed a regular parallel configuration. The relative depth of the horizontal lamellar cut as percentage of the total corneal thickness in the center and periphery was 70.4% ± 4.5% and 55.6% ± 5.9%. Scanning electron microscopy images of the stromal bed showed a relatively smooth surface. Conclusion: The femtosecond laser is effective to prepare a deep horizontal lamellar cut in a standardized method. The stromal bed is smooth and without extensive adjacent tissue damage. The is thinner in the center and thicker at the edges, which may produce a mild hyperopic shift after femtosecond laser-assisted Descemets stripping endothelial keratoplasty.

Organ Culture Preservation for Corneal Tissue

INTRODUCTION The technical and quality aspects of organ culture as a storage method for human donor corneas are described. MATERIALS AND METHODS Data electronically stored since 1989 of > 41,000 corneas, processed in the Cornea Bank Amsterdam, are analysed. The technical information of eye banks collected in the Directory of the European Eye Bank Association (EEBA) is used as comparison. European Union (EU) directive for tissue banking and EEBA technical guidelines are references for the quality aspects. RESULTS Organ culture allows the storage of donor corneas up to 4-5weeks. The storage phase is followed by a generally much shorter phase of 1-7 days, to reverse the corneal swelling occurring in the first phase and to transport the tissue to the clinic. Selection of the corneas based on inspection of the endothelium after storage as well as microbiological testing of the storage solution after a quarantine period are mandatory for this technique. General agreement exists about the outline of the method, but technical variations are applied to suit local circumstances and preferences of corneal surgeons. Agreement exists about a minimum endothelial cell count as selection criterion in case the donor endothelium is meant to be grafted. The use and cutoff points of other selection parameters for the cornea, e.g. the endothelial cell mosaic, are varying. According to EU regulations, a quality management system should be installed. This way each bank is able to issue a standardized product, while the production process is monitored with quality registrations. With the clinical outcome of the graft, the quality of the selection and storage procedures is verified. With the notification of adverse reactions such as primary graft failure and endophthalmitis, minimum risks will be assessed. CONCLUSION The organ-cultured cornea is a well-documented product concerning microbiological safety and quality of the tissue. However, variations in performance and materials and no definite cut-off points for selection do not make an organ-cultured cornea a generally standardized product. The corneal surgeons have to ascertain themselves of the safety and quality of the followed procedure. It is up to an organization such as the EEBA to formulate tissue-specific additions to the EU regulations such as training opportunities, technical guidelines and criteria based on science.

Toxic keratopathy due to the accidental use of chlorhexidine, cetrimide and cialit

Due to economical reasons some ophthalmologists are using an irrigating solution made by the hospital pharmacy instead of the commercially available solutions. These irrigating solutions come in bottles which are identical to the ones used for other solutions. During the last three years bottles were accidentally mixed up five times. Consequently, bottles containing solutions such as chlorhexidine, cetrimide, chlorhexidine/cetrimide and cialit solutions were used during cataract surgery. This resulted in immediate corneal edema which, in its turn resulted in a bullous keratopathy. Four patients underwent a penetrating keratoplasty. In one patient the cornea was covered with a conjunctival flap. Light microscopy of the corneas included epithelial edema, loss of keratocytes, and a disrupted and sometimes absent endothelial cell layer.

Economic Evaluation of Deep Anterior Lamellar Keratoplasty Versus Penetrating Keratoplasty in The Netherlands

PURPOSE To evaluate the cost effectiveness of deep anterior lamellar keratoplasty (DALK) versus penetrating keratoplasty (PK) in The Netherlands. DESIGN Cost-effectiveness analysis alongside a randomized, multicenter clinical trial. METHODS Fifty-three patients with corneal stromal pathologic features not affecting the endothelium were included with 28 patients in the DALK group and 25 in the PK group. Quality of life was measured before surgery and 3, 6, and 12 months after surgery. The main outcome measures were incremental cost-effectiveness ratios per clinically improved patient on the 25-item National Eye Institute Visual Functioning Questionnaire and per patient with endothelial cell loss of maximally 20% within the first year. RESULTS Mean total bootstrapped costs per patient were €7607 (US