Ludwig M. Heindl

A stepwise approach to donor preparation and insertion increases safety and outcome of Descemet membrane endothelial keratoplasty.

Purpose: Lamellar techniques for selective replacement of diseased corneal structures have recently been improved. Descemet membrane endothelial keratoplasty (DMEK) allows the sole replacement of the endothelium-Descemet membrane layer (EDM). However, widespread use of DMEK is currently limited because of problems with donor preparation namely the tearing of the Descemet membrane and the difficulty to unfold the EDM graft in the anterior chamber (AC). Methods: A standardized DMEK procedure that allows safe preparation of EDM, atraumatic introduction of EDM into the AC, reliable orientation of EDM during surgery, and stepwise unfolding within the AC is described in 80 patients. Visual acuity and corneal endothelial cell density were assessed. Results: A stepwise approach using a novel bimanual underwater technique to harvest EDM from donor corneal buttons allows reproducible generation of grafts without tearing the Descemet membrane. Injection of the EDM roll into the AC is achieved by use of a standard injector cartridge, whereas the depth of AC is maintained by an irrigation handpiece. Marks at the margin of EDM allow orientation. Finally, unfolding EDM in the AC is achieved by sequential use of water jets and air bubbles. In the early phase of the learning curve, 4 patients were regrafted because of graft failure. Endothelial cell density decreased from 2600 ± 252 to 1526 ± 341 cells per square millimeter 1 month after DMEK. Conclusions: A novel technique for graft preparation and EDM injection results in improved safety with a high rate of successful DMEKs.

Optimizing Descemet Membrane Endothelial Keratoplasty Using Intraoperative Optical Coherence Tomography

IMPORTANCE Descemet membrane endothelial keratoplasty (DMEK) is a challenging procedure for the surgeon, particularly because of deficient visibility of the delicate tissue due to the natural en face view through the operating microscope. A cross-sectional view would greatly enhance intraoperative overview and enable the surgeon to better control the procedure. OBJECTIVE To retrospectively analyze the use of intraoperative optical coherence tomography (iOCT) for improving the safety of DMEK. DESIGN Intraoperative OCT during DMEK was performed in 26 eyes of 26 patients. We retrospectively analyzed imaging and video data. SETTING Department of Ophthalmology, University of Cologne. PARTICIPANTS Seven men and 19 women aged 39 to 93 years with corneal endothelial dysfunction undergoing DMEK. EXPOSURE Descemet membrane endothelial keratoplasty. MAIN OUTCOMES AND MEASURES Visibility of surgical steps, overall duration of DMEK, overall time for complete intraoperative air filling of the anterior chamber, and correlation between donor age and Descemet rolling behavior. RESULTS Intraoperative OCT enables visualization of all steps of the DMEK procedure. Overall mean (SD) duration of the DMEK procedure was 25.7 (6.9) minutes when using iOCT. Overall mean (SD) complete intraoperative anterior chamber air-filling time was 236 (108) seconds in contrast to 60 to 90 minutes for standard air-filling time. Descemet membrane rolling behavior showed significant inverse correlation between donor age (range, 39-93 years) and the extent of rolling (R2 = 0.5 [P = .006]). CONCLUSIONS AND RELEVANCE Intraoperative OCT enhances the visibility of graft orientation and unfolding, thereby improving safety of the DMEK procedure. Overall, iOCT is a helpful device that may support surgeons in all steps of DMEK procedures.

Novel anti(lymph)angiogenic treatment strategies for corneal and ocular surface diseases

The cornea is one of the few tissues which actively maintain an avascular state, i.e. the absence of blood and lymphatic vessels (corneal [lymph]angiogenic privilege). Nonetheless do several diseases interfere with this privilege and cause pathologic corneal hem- and lymphangiogenesis. The ingrowths of pathologic blood and lymphatic vessels into the cornea not only reduce transparency and thereby visual acuity up to blindness, but also significantly increases the rate of graft rejections after subsequent corneal transplantation. Therefore great interest exists in new strategies to target pathologic corneal (lymph)angiogenesis to promote graft survival. This review gives an overview on the vascular anatomy of the normal ocular surface, on the molecular mechanisms contributing to the corneal (lymph)angiogenic privilege and on the cellular and molecular mechanisms occurring during pathological neovascularization of the cornea. In addition we summarize the current preclinical and clinical evidence for three novel treatment strategies against ocular surface diseases based on targeting pathologic (lymph)angiogenesis: (a) modulation of the immune responses after (corneal) transplantation by targeting pathologic (lymph)angiogenesis prior to and after transplantation, (b) novel concepts against metastasis and recurrence of ocular surface tumors such as malignant melanoma of the conjunctiva by anti(lymph)angiogenic therapy and (c) new ideas on how to target ocular surface inflammatory diseases such as dry eye by targeting conjunctival and corneal lymphatic vessels. Based on compelling preclinical evidence and early data from clinical trials the novel therapeutic concepts of promoting graft survival, inhibiting tumor metastasis and dampening ocular surface inflammation and dry eye disease by targeting (lymph)angiogenesis are on their way to translation into the clinic.

Split Cornea Transplantation : Relationship between Storage Time of Split Donor Tissue and Outcome

PURPOSE To analyze the relationship between storage time of split donor tissue and outcomes after deep anterior lamellar keratoplasty (DALK) and Descemets membrane endothelial keratoplasty (DMEK). DESIGN Retrospective analysis of a nonrandomized, consecutive, interventional case series. PARTICIPANTS One hundred ten eyes with anterior stromal disease suitable for DALK and 110 eyes with endothelial disease suitable for DMEK underwent surgically successful split cornea transplantation combining both procedures within 7 days after splitting. METHODS Split donor storage times (splitting to grafting) and total storage times (death to grafting) were correlated with the 1-year functional and morphologic outcomes after DALK and DMEK surgery using a Spearman correlation coefficient and a Mann-Whitney U test. MAIN OUTCOME MEASURES Best spectacle-corrected visual acuity (BSCVA), endothelial cell density, and complication rates within 12 months of follow-up. RESULTS The mean split donor storage time was 35 ± 47 hours (range, 0-162 hours) after splitting for anterior donor grafts and 21 ± 40 hours (range, 0-158 hours) for posterior grafts. The mean total storage time was 352 ± 108 hours (range, 108-678 hours) for anterior lamellas and 339 ± 109 hours (range, 96-630 hours) for posterior lamellas. One year after DALK, the mean BSCVA was 20/30 (range, 20/50-20/20), endothelial cell loss was 8% (range, 2%-16%), and the complication rate (Descemets folds, epitheliopathy, loose sutures) was 18%. One year after DMEK, the mean BSCVA was 20/25 (range, 20/40-20/16), endothelial cell loss was 41% (range, 17%-63%), and the complication rate (partial graft detachment) was 62%. For DALK and DMEK, no significant association was observed between split donor storage time as well as total storage time and BSCVA (P ≥ 0.409), endothelial cell loss (P≥0.236), or complication rate (P ≥ 0.647) within 1 year of follow-up. CONCLUSIONS Anterior and posterior donor tissue may be stored safely for up to 1 week in organ culture before use in DALK and DMEK surgery. This simplifies the clinical feasibility of split cornea transplantation to reduce donor shortage and cost in corneal transplantation in the future. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Histologic Analysis of Descemet Stripping in Posterior Lamellar Keratoplasty

OBJECTIVE To investigate how precise Descemet stripping works in posterior lamellar keratoplasty (Descemet stripping automated endothelial keratoplasty [DSAEK]) for the treatment of corneal endothelial disorders. METHODS In a prospective, single-center, nonrandomized consecutive series, 20 Descemet membrane specimens obtained after Descemet stripping in DSAEK using a Price hook were examined using histologic analysis and transmission electron microscopy for the presence of residual stroma, thickness of the Descemet membrane, endothelial cell count, and presence of guttae or a posterior collagenous layer. Pathologic findings were correlated with the underlying clinical disease. RESULTS Light and electron microscopy revealed no evidence of adherent rests of corneal stroma in all 20 specimens after Descemet stripping. The mean (SD) total thickness of the Descemet membrane was 21.5 (4.5) microm in peripheral localization and 17.6 (3.8) microm in central localization. The anterior banded layer measured a mean (SD) of 3.0 (0.8) microm thick; the posterior nonbanded layer, 16.7 (5.2) microm thick. The mean (SD) endothelial cell count was 1.7 (1.4) cells per high-power field. Guttae were seen in 15 specimens (75%), and a posterior collagenous layer was found in 3 (15%). CONCLUSION Descemet stripping in DSAEK using the Price hook achieves complete and specific removal of the Descemet membrane without adherent stroma in different underlying endothelial pathologic abnormalities.

Tumors of the Lacrimal Drainage System

Tumors of the lacrimal drainage system are rare, but potentially life-threatening. They comprise a large and variable spectrum of entities grouped into three major categories of primary epithelial, primary nonepithelial and inflammatory lesions. The most common primary epithelial tumors include papilloma, squamous cell carcinoma and transitional cell carcinoma, the most frequent primary nonepithelial tumors fibrous histiocytoma, malignant lymphoma and malignant melanoma, and the most common inflammatory lesions sarcoidosis, Wegener granulomatosis and pyogenic granuloma. This review outlines the incidence, types, management and prognosis of tumors affecting the lacrimal drainage system.

Optimising deep anterior lamellar keratoplasty (DALK) using intraoperative online optical coherence tomography (iOCT)

Background/aims To describe the use of intraoperative online optical coherence tomography (iOCT) for improving deep anterior lamellar keratoplasty (DALK) surgery. Methods Retrospective case series of 6 eyes of 6 male patients with keratokonus, corneal dystrophy or herpetic stromal scars undergoing DALK were investigated using intraoperative optical coherence tomography and postsurgical image/video analysis. Main outcome measures were: visibility of surgical steps, especially, assessment of placement depth of injection needle, preparation of bare Descemets membrane and drainage of interface fluid. Results iOCT enables real-time visualisation of all surgical steps of DALK procedure in all patients. Placement of air injection needle above Descemets membrane was reliably monitored as was presence of bare Descemets membrane and potential interface fluid. Conclusions iOCT assists with visualisation of injection needle placement and with assessment of bare Descemets membrane as well as interface fluid during the DALK procedure. Overall iOCT may be a helpful device that supports surgeons in all steps of DALK procedure.

Immunreaktionen nach DMEK, DSAEK und DALK

PURPOSE The aim of this study is to describe incidence, diagnosis and therapy for endothelial immune reactions after modern lamellar corneal transplantat surgery (DMEK, DSAEK, DALK). METHODS A PubMed-based literature review and our own clinical and experimental data are evaluated. RESULTS There is no longer an endothelial immune reaction after DALK for keratoconus. DMEK significantly reduces the risk for endothelial immune reactions after surgery for Fuchs dystrophy. CONCLUSIONS Modern lamellar corneal transplant techniques such as DALK and DMEK have nearly abolished the risk for endothelial immune reactions in the avascular recipient bed.

Intraocular Tumor-Associated Lymphangiogenesis: A Novel Prognostic Factor for Ciliary Body Melanomas with Extraocular Extension?

PURPOSE To evaluate whether intraocular tumor-associated lymphangiogenesis contributes to prognosis of ciliary body melanomas with extraocular extension and to study its association with other tumor characteristics. DESIGN Nonrandomized, retrospective case series. PARTICIPANTS Twenty consecutive patients enucleated for a malignant melanoma of the ciliary body with extraocular extension. METHODS Lymphatic vessels were identified using lymphatic vascular endothelial-specific hyaluronic acid receptor-1 (LYVE-1) and podoplanin as specific immunohistochemical markers for lymphatic vascular endothelium. Baseline tumor characteristics included intra- and extraocular tumor size, 2009 tumor, node, metastasis (TNM) classification, route of extraocular spread, tumor cell type, mitotic rate, Ki-67 proliferation-index, microvascular patterns and density, tumor-infiltrating lymphocytes and macrophages, and expression of human leukocyte antigen (HLA) class I and insulin-like growth factor-1 receptor. Kaplan-Meier and Cox regression analyses of melanoma-specific survival were performed. MAIN OUTCOME MEASURES Prevalence of intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels and association with intraocular tumor characteristics and metastasis-free survival. RESULTS Intraocular LYVE-1(+) and podoplanin(+) lymphatic vessels could be detected in 12 (60%) of 20 ciliary body melanomas with extraocular extension. Presence of intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels was significantly associated with larger intra- (P = 0.002) and extraocular tumor size (P<0.001), higher TNM categories (P = 0.004), epithelioid cellularity (P = 0.016), higher mitotic rate (P = 0.003), higher Ki-67 proliferation-index (P = 0.049), microvascular networks (P = 0.005), higher microvascular density (P = 0.003), more tumor-infiltrating macrophages (P = 0.002), higher expression of HLA class I (P = 0.046), and insulin-like growth factor-1 receptor (P = 0.033), but not significantly with route of extraocular spread (P = 0.803), and tumor-infiltrating lymphocytes (P = 0.069). Melanoma-specific mortality rates increased significantly with the presence of intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels (P = 0.008). By multivariate Cox regression, tumor size (hazard ratio, 14.40; P = 0.002), and presence of intraocular lymphatic vessels (hazard ratio, 8.09; P = 0.04) were strong prognostic predictors of mortality. CONCLUSIONS Intraocular peritumoral lymphangiogenesis seems to be associated with an increased mortality risk in patients with ciliary body melanomas and extraocular extension. This association may be primarily because of an association of intraocular lymphangiogenesis with greater tumor size and increased malignancy.

Prognostic Significance of Tumor-Associated Lymphangiogenesis in Malignant Melanomas of the Conjunctiva

PURPOSE To evaluate whether tumor-associated lymphangiogenesis contributes to prognosis of conjunctival malignant melanomas and to study its association with other tumor characteristics. DESIGN Nonrandomized, retrospective case series. PARTICIPANTS A total of 109 consecutive patients with primary conjunctival malignant melanoma. METHODS Proliferating lymphatic vessels were identified immunohistochemically using lymphatic vascular endothelial hyaluronan receptor-1 and podoplanin as specific lymphatic endothelial markers and Ki-67 as proliferation marker. Baseline tumor characteristics included tumor location, tumor thickness, tumor diameter, tumor origin, and tumor growth pattern. Kaplan-Meier and Cox regression analyses of the risk of local recurrence, lymphatic spread, distant metastasis, and melanoma-related death were performed. MAIN OUTCOME MEASURES Intratumoral lymphatic vascular density and its association with tumor characteristics and recurrence-free, lymphatic spread-free, distant metastasis-free, and melanoma-specific survival. RESULTS Intratumoral and peritumoral proliferating lymphatic vessels could be detected in all of the 109 conjunctival melanoma samples. High intratumoral lymphatic density was significantly associated with palpebral tumor location (P<0.001), greater tumor thickness (P<0.001), larger tumor diameter (P = 0.001), tumor origin de novo (P = 0.002), and nodular tumor growth pattern (P = 0.037). Patients with high intratumoral lymphatic density revealed significantly lower recurrence-free, lymphatic spread-free, distant metastasis-free, and melanoma-specific survival rates (P<0.001 for all). By multivariate Cox regression, factors predictive of local recurrence included palpebral tumor location (hazard ratio [HR] 2.66, P = 0.014), large tumor diameter (HR 5.48, P<0.001), and high intratumoral lymphatic density (HR 2.48, P = 0.043); factors predictive of lymphatic spread included palpebral tumor location (HR 4.13, P = 0.009), high tumor thickness (HR 12.17, P<0.001), and high intratumoral lymphatic density (HR 6.79, P = 0.019); factors predictive of distant metastasis included palpebral tumor location (HR 7.63, P<0.001), high tumor thickness (HR 8.60, P<0.001), large tumor diameter (HR 0.30, P = 0.029), and high intratumoral lymphatic density (HR 8.90, P = 0.047); and factors predictive of melanoma-related death included palpebral tumor location (HR 7.74, P<0.001), high tumor thickness (HR 10.88, P<0.001), large tumor diameter (HR 0.28, P = 0.018), and, with borderline significance, high intratumoral lymphatic density (HR 8.46, P = 0.052). CONCLUSIONS Tumor-associated lymphangiogenesis seems to be associated with an increased risk of local recurrence, lymphatic spread, distant metastasis, and melanoma-related death in patients with conjunctival malignant melanomas. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.