Indentation of the cornea: A Bi-layer contact problem.

Histological observations of the cornea have identified the presence of multiple layers with differing thickness and function. The composition of the cornea consists primarily of collagen fibrils held together with proteoglycans but with an aqueous interstitial component being dominant. Indentation provides a means to quantify the spatial variation of the mechanical properties of the cornea, however the role of the different layers on the indentation response has barely been addressed. In addition, the response of the fluid content and its displacement during indentation has not been adequately considered. In this study indentation of the cornea with a relatively large spherical tipped indenter (R = 500 µm) is considered. It was observed that the initial phase of loading did not fit a classic Hertz elastic response but showed an initial steeper slope that gradually declines with increasing force and displacement. A relatively simple approach is developed that initially considers the cornea as a poro-elastic bi-layer contact problem, that is the presence of an outer thin stiffer Bowman's layer overlaying the thicker less stiff stroma.

Toric IOL positioning with a no-touch head-up display axis alignment.

PURPOSE: To compare a new no-touch alignment technique for toric intraocular lenses (IOL) with the conventional technique that uses a manual pendulum. METHODS: In this retrospective case-control study, patients who underwent toric IOL implantation using two different alignment techniques (digital Callisto® system vs. manual-pendulum-based marking) were compared in a vector analysis using the Alpins method and an analysis of variance regarding corrected and uncorrected visual acuity and the deviation of the achieved IOL axis from the targeted axis. RESULTS: Sixty-one eyes were included into analysis. Thirty-six of these surgeries were performed via the Callisto® system and 25 eyes via pendulum-based corneal markings. Median IOL axis misalignment was 3° in both groups. Median uncorrected distance visual acuity was 0.097 logMAR versus 0.200. Median best-corrected visual acuity was 0.000 logMAR versus 0.097. All these data were below the range of statistical significance (p > 0.05). Vector analysis showed no significant difference for TIA [median of 3.14 diopters (D) vs. 2.73 D], SIA (median of 3.82 D vs. 3.79 D), DV (1.18 D vs. 1.08 D), and CI (1.23 vs. 1.29). Median angle of error was 1.96° versus - 0.44° (p > 0.05). CONCLUSIONS: We found no significant difference in the refractive results, the IOL positioning, and the best-corrected and uncorrected distance visual acuity between the two compared methods. Nevertheless, the Callisto® IOL alignment system delivers a standardized and easy-to-use technology. In particular, less-experienced surgeons might benefit from this marking technique.

[New biomaterials and alternative stem cell sources for the reconstruction of the limbal stem cell niche]. / Evaluierung neuer Biomaterialien und alternativer Stammzellpopulationen zur Rekonstruktion der Limbusstammzellnische.

Reconstruction of the limbal stem cell niche in patients with limbal stem cell insufficiency remains one of the most challenging tasks in the treatment of ocular surface diseases. Ex vivo expansion of limbal stem cells still has potential for optimization despite positive reports in centers worldwide. New biomaterials as well as alternative cell sources for the reconstruction of the limbal stem cell niche have been published in recent years. The aim of this review is to provide insight into new biomaterials and cell sources which may find their way into clinical routine in the upcoming decades.

A simple basis for determination of the modulus and hydraulic conductivity of human ocular surface using nano-indentation.

This paper presents a simple analysis based upon Darcy's Law and indentation contact mechanics to determine the effective hydraulic conductivity and elastic modulus of fluid filled tissues. The approach is illustrated with the mechanical response of the human ocular surface using a 500µm radius spherical tipped indenter. Indentations of various regions of the ocular surface including the corneal stroma, limbal region and sclera have been conducted. Force-control indentations were made to a maximum force, which was maintained before unloading. Measurements of the indentation response of cornea at three different loading rates were also made. Elastic like response was observed during loading, which was followed by extensive creep prior to unloading. STATEMENT OF SIGNIFICANCE: This manuscript attempts to provide a relatively simply model for the contact loading of fluid containing tissues and materials. It shows that the response of such materials provides a basis for determining the effective modulus and effective hydraulic conductivity (permeability) in much the same manner that hardness and modulus do for the indentation of elastic-plastic materials. Eye tissue with its anisotropic elastic and permeability properties is used to illustrate the approach.

[Surgical removal of Salzmann's nodules using intraoperative mitomycin C]. / Chirurgische Abtragung von Salzmann-Knoten unter Anwendung von intraoperativem Mitomycin C.

Salzmann's nodules comprise a heterogeneous group of greyish superficial corneal opacities. A substantial percentage is most likely caused by dystrophies. This could explain the recurrences after surgical removal. The Eye Center of the University Hospital Freiburg has been using mitomycin C intraoperatively during surgical removal of Salzmann's nodules since 2007 to prevent recurrences. We recently performed an uncontrolled prospective trial to evaluate this approach and also reviewed the literature. Worldwide, a total of 38 eyes have been treated with mitomycin C during surgery for Salzmann's nodules. No recurrences have been reported so far with follow-up exceeding at least 2 years in almost all eyes. No severe side effects have been observed to date. We therefore think that mitomycin C during surgery for Salzmann's nodules is advisable despite the lack of evidence from a randomized clinical trial. However, all patients must consent to the off label use of mitomycin C.

Outcomes of Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty from a single centre study.

PURPOSE: According to some pioneer surgeons, lamellar endothelial keratoplasty techniques (EK), including Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK), yield excellent clinical results. However, there is a lack of studies with high levels of evidence and results of large national keratoplasty registers are contradictory. Therefore, two large cohorts of DMEK and DSAEK procedures are compared to a cohort of penetrating keratoplasty (PK). METHODS: The study reports 868 keratoplasty procedures at a single centre (694 eyes with Fuchs endothelial dystrophy (FED) and 174 with bullous keratopathy (BK)). Patients underwent DMEK (450 eyes), DSAEK (89 eyes), or PK (329 eyes). Postoperative visual acuity, endothelial cell density (ECD), rate of regrafting, and rejections were recorded. RESULTS: Visual acuity recovers faster and to a greater extent in EK compared to PK. DMEK performs better than DSAEK. ECD drops faster initially for EK compared to PK. In EK the rate of regrafting is higher than in PK (7 % in DMEK, 20 % in DSAEK and 2 % in PK in FED). The rejection rate is lowest following DMEK (7 % after DMEK, 21 % after DSAEK and 18 % after PK in FED). CONCLUSIONS: In contrast to recent reports from national keratoplasty registers, the overall clinical outcome of EK in FED and BK is superior to PK. Including ocular comorbidities and learning curves, these data reflect a realistic setting for comparing the different keratoplasty techniques. Corneal surgeons may be encouraged to preferentially use DMEK in FED and BK.

[Patient-Centred Care of Ocular Graft-vs-Host Disease in Germany]. / Versorgungsstrukturen der okulären Graft-versus-Host Disease in Deutschland.

BACKGROUND: Ocular GvHD is a severe complication following allogenic blood stem cell transplantation leading to massive reduction in quality of life and ocular pathologies including corneal perforation. Interdisciplinary patient-centred care needs to be performed in specialized ophthalmic centers that provide all diagnostic and therapeutic options, however, only few clinics have the necessary infrastructure. In addition there is a lack of transparency and easily accessible information for the patients regarding ophthalmic care and specialized centres. For this reason the "Ocular GvHD working group" within the Cornea Section of the German Society of Ophthalmology has been founded to evaluate and improve patient-centered care in ocular GvHD within Germany. METHODS: A survey was performed among the members of the Cornea Section of the German Society of Ophthalmology and the Directors of Departments of Ophthalmology in Germany that evaluated the number of annual examinations, presence of specialized GvHD outpatient clinics and eye screenings prior to allogenic blood stem cell transplantation (aBSCT). RESULTS: 25 clinics (19 university hospitals, 6 general hospitals) responded to the survey. In 18 clinics aBSCT are performed. Between 5 and 200 patients after aBSCT are examined per year per clinic. Larger institutions are associated with departments of haemato-oncology and other specialised disciplines to facilitate an interdisciplinary patient care. Three clinics are associated with GvHD competence centres. The major challenge in establishing an appropriate infrastructure for better patient-centered care is the limited or lacking reimbursement by health insurances. CONCLUSIONS: Within Germany only few ophthalmic centres exist that provide state-of-the-art patient-centered care for ocular GvHD. The present structures are not sufficient to treat all patients undergoing aBSCT following existing guidelines. Joint efforts are necessary to establish more and accessible competence centers for ocular GvHD with sufficient personnel and structural resources. In addition, ocular GvHD should be included as a mandatory topic in medical training and transparent and easily accessible information needs to be provided for patients and health-care professionals.

[Current and future therapeutic options in limbal stem cell insufficiency]. / Aktuelle und zukünftige therapieoptionen bei erkrankungen der limbusstammzellen.

Therapy for limbal stem cell insufficiency (LSCI) is one of the most challenging tasks in ocular surface surgery. Partial and unilateral LSCI can be treated by fractionated abrasion or autologous limbal stem cell transplantation from the fellow eye. In cases of advanced bilateral and partial LSCI, transplantation of ex vivo expanded sheets of limbal stem cells on amniotic membrane or fibrin may be performed. All patients with complete bilateral LSCI must rely on allogenic limbal stem cell transplantation comprising higher immunological risks. Progress using this technique has been achieved by the application of mitomycin C and amniotic membrane. Alternatively, transplantation of ex vivo expanded oral mucosal sheets may be used in bilateral LSCI, but only few long-term data are available on this technique as yet. While experimental attempts to use transdifferentiated bone marrow stem cells as a substitute for corneal epithelial cells have been without success, transdifferentiation of hair follicle stem cells to corneal epithelial cells may be more promising due to the identical lineage. But these experiments have not gone beyond the in vitro stage yet.

[Ocular surface reconstruction in limbal stem cell insufficiency: transplantation of limbal tissue]. / Oberflächenrekonstruktion bei Limbusstammzellinsuffizienz : Transplantation von Limbusgewebe.

Reconstruction of the ocular surface in patients with limbal stem cell insufficiency (LSI) remains one of the most challenging tasks in ophthalmology. The transplantation of lamellar limbal tissue in total LSI represents an established therapeutic concept, while an abrasion of the conjunctival pannus allowing normal limbal epithelium to recolonize the cornea is the treatment of choice in partial LSI. Surgery must be postponed until an inflammation-free period is reached and lid abnormalities have been corrected. In unilateral total LSI autologous limbal tissue from the healthy eye is transplanted in order to circumvent immunological adverse events. In bilateral total LSI cadaveric or living related allogenic limbal tissue is used for transplantation, in which case systemic immunosuppression and HLA matching are mandatory. The combination with amniotic membrane transplantation and mitomycin C treatment can further improve long-term outcome of limbal stem cell transplantation.

[Perspectives and current state in limbal stem cell transplantation]. / Perspektiven und aktueller Stand der Limbusstammzelltransplantation.

The transplantation of limbal stem cells is one of the most challenging surgical approaches in ocular surface reconstruction. Partial and unilateral limbal stem cell insufficiency (LSCI) can be treated by fractionated abrasion or autologous limbal stem cell transplantation from the fellow eye. In cases of advanced bilateral and partial LSCI, ex vivo expansion of limbal stem cells on amniotic membranes or fibrin can be performed but all patients with complete bilateral LSCI must rely on allogenic limbal stem cell transplantation with high immunological risks. Attempts to combine allogenic limbal stem cell transplantation with mitomycin C and amniotic membrane transplantation are promising. In the laboratory, attempts to transdifferentiate bone marrow stem cells into corneal epithelial cells have been without success. Nonetheless, transdifferentiation of hair follicle stem cells into corneal epithelial cells looks promising. In parallel, research on the limbal stem cell niche is ongoing to elucidate the natural environment of limbal stem cells in order to improve ex vivo culture.

[Intensive intracorneal keloid formation in a case of Peters plus syndrome and in Peters anomaly with maximum manifestation]. / Ausgeprägte intrakorneale Keloidbildung bei Peters-Plus-Syndrom und bei einer Maximalvariante der Peters-Anomalie.

We present two cases of Peters anomaly (Peters plus syndrome and a maximum manifestation variant) with abnormally thickened cornea and corneal staphyloma. Both patients presented to our hospital shortly after birth and were treated with perforating keratoplasty and lensectomy. Histological analysis showed marked thickening of the corneal stroma due to abnormal stromal connective tissue deposition. Additionally, both eyes showed the characteristic changes of Peters anomaly with corneal opacity, adherence of the iris stroma and anterior lens surface to the posterior corneal surface, absence of the corneal endothelium, Descemet and Bowmans layers. Peters anomaly with abnormally thick intracorneal fibrosis with or without congenital corneal staphyloma is a very rare manifestation.

[Isolated corneal intraepithelial dysplasia]. / Isoliertes Carcinoma in situ der Kornea.

We present the case of an 83-year-old patient with an isolated epithelial dysplasia of the cornea. After corneal abrasion the lesion reoccurred 14 days later. The abrasion was then increased to cover the whole corneal epithelium and adjacent limbal and conjunctival areas were also biopsied. Histology revealed a corneal epithelial dysplasia stage 3, whereas the limbal and conjunctival biopsies showed normal epithelium. After resection two cycles of local mitomycin C application (2 cycles of 14 days each) were administered and 9 months after the second intervention the cornea remained clear with good vision. The investigation for human papillomavirus showed a type 6, which is not associated with an increased risk of malignancy.

[Corneal melting after cross-linking and deep lamellar keratoplasty in a keratoconus patient]. / Hornhauteinschmelzung nach Cross-Linking und tiefer lamellärer Keratoplastik ("DALK") bei Keratokonus.

We present the case of a 45-year-old patient with severe atopic disease and keratoconus who suffered from corneal melting following cross-linking and deep anterior lamellar keratoplasty (DALK) due to subclinical infection with Herpes simplex virus (HSV). Penetrating keratoplasty and intensive antiviral and immunosuppressive medical treatment were necessary to control the infection. The case demonstrates the difficulties in the treatment of keratoconus in patients with severe atopic disease.

Perforation rosette of the lens after Nd:YAG laser iridotomy.

PURPOSE: To describe an unreported complication of Nd:YAG laser iridotomy. METHODS: We examined a 31-year-old patient with pigment dispersion syndrome and moderately increased intraocular pressure whose left eye had been treated prophylactically with Nd:YAG laser iridotomy and who complained of blurred vision thereafter. RESULTS: Slit-lamp examination of the left eye disclosed a typical perforation rosette of the posterior pole of the crystalline lens with a perforation of the anterior lens capsule under the iridotomy site and pigment within the lens. Opacity regressed spontaneously, and vision returned to normal. CONCLUSIONS: A perforation rosette of the lens can occur after Nd:YAG laser iridotomy and should be considered a possible serious complication of the procedure.

Intracorporeal lithotripsy with the Alexandrite laser.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate clinical use of an Alexandrite laser lithotripter for intracorporeal lithotripsy of urinary calculi. STUDY DESIGN/MATERIALS AND METHODS: We prospectively evaluated a flash lamp pumped, Q-switched Alexandrite solid-state laser for use in conjunction with ureteroscopy (30 cases) or percutaneous nephrolithotripsy (2 cases). The laser operates at a wavelength of 755 nm in a pulsed mode with pulses of 150-800 ns duration at energy settings of 30-80 mJ. RESULTS: The fragmentation rate with the Alexandrite laser alone was 50% (16/32). Failure of the laser was due to equipment malfunction or technical problems in 11 cases and inability to fragment the stone in 5. All cases of failed Alexandrite laser lithotripsy were successfully salvaged with alternative modalities of endoscopic stone destruction and removal. One intraoperative complication, a ureteral perforation, occurred; however, no long-term sequelae related to laser use was documented. CONCLUSION: Clinical results with the Alexandrite laser appear to be inferior to those reported with Alternative laser systems and other forms of intracorporeal lithotripsy. Whereas some of the inadequacies we have noted may be addressed in the future by modifications in the unit and delivery systems, we would not recommend this device for intracorporeal lithotripsy of urinary calculi in its current form.

Preliminary experience with holmium: YAG laser lithotripsy.

Lithotripsy with the pulsed-dye laser has been shown to be a safe and effective method of intracorporeal urinary stone fragmentation. Recently, a new device, the holmium: YAG laser, has been developed with both soft tissue and lithotripsy applications. We present our preliminary experience with the Ho:YAG laser for lithotripsy of urinary calculi. Ureteroscopy and lasertripsy resulted in successful fragmentation of ureteral stones in 92% of 21 patients when the laser was used alone or in combination with electrohydraulic lithotripsy. One complication directly related to the use of the laser occurred, a ureteral perforation, when the device was utilized under fluoroscopic control. In four patients undergoing percutaneous flexible nephrolithotripsy, the laser demonstrated utility in fragmenting caliceal stones remote from the nephrostomy tract. In summary, the Ho:YAG laser has demonstrated its efficacy as a method of intracorporeal lithotripsy. The tissue effects of this device, as well as the optimal energy/pulse and frequency settings, need further evaluation in order to minimize the risks of tissue injury.

Investigation of the tissue effects of a new device for intracorporeal lithotripsy--the Swiss Lithoclast.

Currently three modalities are available for intracorporeal stone fragmentation--electrohydraulic, ultrasound and laser lithotripsy. A new device, the Swiss Lithoclast, has been developed by the Departments of Medical Electronics and Urology at the University of Lausanne, Switzerland. This device has been used clinically in several countries for the treatment of stones throughout the human urinary tract. While no adverse outcomes have been reported, the potential tissue effects of the device have not been thoroughly investigated in an animal model. The objective of the present study is to evaluate the possible acute and long-term tissue effects of this instrument on the pig urinary tract. In all acute animals, visible mucosal lesions were seen at the site of probe firing in the bladders and ureters. Histologic examination demonstrated the effects of acute trauma with edema, hemorrhage and mucosal denudation. No significant long-term tissue effects were noted either pathologically or on radiographs in the 3- and 6-week animals. This study confirms our clinical impression that the Swiss Lithoclast effectively fragments urinary calculi and is associated with a large margin of safety.

Sarcomatoid renal cell carcinoma. An immunohistochemical study of 18 cases.

Malignant spindle cell neoplasms are a diagnostic challenge regardless of their location. In the retroperitoneum a major consideration in the differential diagnosis is sarcomatoid renal cell carcinoma; if an epithelial component cannot be recognized histologically, special studies may be required to reach the correct diagnosis. In an attempt to better characterize this entity, 23 cases of sarcomatoid renal cell carcinoma (6.3%) were identified from a review of 363 renal cell carcinomas. Blocks were available for immunohistochemical analysis in 18 cases. The epithelial and sarcomatoid portions were studied with a panel of antibodies directed against cytokeratin (AE1/AE3, CAM 5.2, and 34 beta E12), epithelial membrane antigen, Leu-M1, muscle-specific actin, S100 protein, desmin, and vimentin. The epithelial nature of the spindle cell component was best demonstrated by positive reactivity with the anti-cytokeratin AE1/AE3 (in 17 [94%] of the 18 cases). The other epithelial markers stained the spindle cell component less frequently: cytokeratin CAM 5.2 in seven cases (39%); epithelial membrane antigen in nine cases (50%); and high-molecular-weight cytokeratin 34 beta E12 in no cases (0%). In 10 cases (56%) vimentin positivity and in six cases (33%) actin positivity was seen in the spindled areas. The spindle cell component stained for Leu-M1 in four cases (22%) and for S100 protein in one case (6%) and did not react for desmin in any case. From this study we conclude that in the majority of sarcomatoid renal cell carcinomas the epithelial nature of the spindle cells, as indicated by cytokeratin expression, can be documented using immunohistochemical methods.

Transitional cell carcinoma of the renal pelvis with choriocarcinomatous differentiation. Immunohistochemical and immunoelectron microscopic assessment of human chorionic gonadotropin production by transitional cell carcinoma of the urinary bladder.

BACKGROUND: There have been 12 documented cases of choriocarcinoma arising in the urinary bladder, either alone or in combination with other epithelial tumors. It has been shown that some high-grade transitional cell carcinomas (TCC), without obvious syncytiotrophoblastic elements, can produce human chorionic gonadotrophins (HCG). METHODS: A case of choriocarcinoma, in association with high-grade TCC of the renal pelvis, was encountered in an 80-year-old man. For additional evaluation of HCG production by TCC, 25 consecutive cases of invasive high-grade TCC of the bladder were stained with an anti-HCG antibody. Immunogold staining also was performed in two of the cases studied. RESULTS: Immunoperoxidase staining of the renal pelvis tumor showed focal positivity for HCG within the TCC and a more intense reaction as the tumor cells differentiated into choriocarcinoma elements. Seven of the 25 cases (28%) displayed varying degrees of reactivity within individual cells or groups of cells. In an additional case, typical syncytiotrophoblastic giant cells without cytotrophoblasts were seen in a high-grade TCC. Immunogold studies demonstrated positive labeling in the cytoplasm of carcinoma cells in a case of TCC without syncytiotrophoblasts and in the syncytiotrophoblastic giant cells in the one case in which these were present. CONCLUSIONS: The findings support a metaplastic origin of cases of choriocarcinoma arising primarily in the urothelial tract.