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Alice L Yu,1 Michaela Kaiser,1 Markus Schaumberger,1 Elisabeth Messmer,1 Daniel Kook,1 Ulrich Welge-Lussen2 1Department of Ophthalmology, Ludwig-Maximilians-University, Munich, 2Department of Ophthalmology, Friedrich-Alexander-University, Erlangen, Germany Purpose: In this study, we assessed the outcome of penetrating keratoplasties using organ-cultured corneal tissues at the University Eye Hospital, Ludwig-Maximilians-University, Munich, Germany. The goal was to identify perioperative and postoperative risk factors that may affect graft survival.Patients and methods: The medical records of 377 patients who underwent a penetrating keratoplasty between 2001 and 2011 were reviewed. Organ-cultured corneal tissue was obtained from the eye bank of Ludwig-Maximilians-University. Perioperative and postoperative risk factors for graft failure were evaluated by univariate and multivariate analyses.Results: The 5-year overall survival rate of penetrating keratoplasties was 68%. Graft failure occurred in 26% of patients. High-risk keratoplasties, such as repeat penetrating keratoplasties and emergency penetrating keratoplasties, as well as postoperative conditions, such as glaucoma, retinal surgery, suture problems, persistent epithelial defect, infectious keratitis, and graft rejection, were significantly associated with graft failure in the multivariate analyses.Conclusion: This study showed a similar graft-survival rate as demonstrated in previous studies. In addition, a number of perioperative and postoperative risk factors were identified in this specific patient population. Keywords: penetrating keratoplasty, graft failure, risk factor, cornea bank

Purpose:To evaluate the surgical results of pars plana vitrectomy with peeling of the inner limiting membrane (ILM) in a preliminary series of 12 eyes with diffuse diabetic macular edema.Patients and Methods:Pars plana vitrectomy with peeling of the ILM was performed in 12 eyes with diffuse diabetic

The onset of peripheral ulcerative keratitis in the course of a connective tissue disorder, such as rheumatoid arthritis, relapsing polychondritis, or systemic lupus erythematosus, may reflect the presence of potentially lethal systemic vasculitis. Moreover, peripheral ulcerative keratitis may be the first sign of systemic necrotizing vasculitis in patients with Wegener's granulomatosis, polyarteritis nodosa, microscopic polyangiitis, or Churg-Strauss syndrome. Although the exact pathogenesis of this severe corneal inflammation and destruction is not well understood, evidence points to a dysfunction in immunoregulation with immune complexes formed in response to autoantigens or to some unknown microbial antigen depositing in scleral and limbal vessels. These events lead to changes that are mainly responsible for the resulting tissue damage. In pauci-immune vasculitides positive for antineutrophil cytoplasmic antibodies, cell-mediated cytotoxicity may play an important role in the pathogenesis of peripheral ulcerative keratitis. Untreated systemic conditions such as those mentioned above may carry a grave prognosis for the eye and may also be life-threatening. Immunosuppressive therapy with corticosteroids and cytotoxic agents is, we believe, mandatory in the treatment of these multisystem disorders associated with vasculitic peripheral ulcerative keratitis.

Background: Recent studies have raised confusion about the fluorescein angiographical and histopathological correlation of CNV.

Sterile keratitis shows multiple manifestations. It may occur as an ophthalmological problem but can also be part of a systemic disease, including potentially lethal systemic vasculitis. Diagnosis as well as management of this disease is a challenging task for the ophthalmologist. There are therapeutic principles which apply to all non-infectious cases of keratitis and corneal ulcerations. Specific treatments, however, are determined by the pathogenesis and may differ. Therefore, an accurate diagnosis must guide therapeutic decision making. The correct diagnosis and management of sterile ulcerative keratitis is able to restore the patient's vision in most cases. In potentially lethal systemic disease it may even be able to save the patient's life.Sterile Keratitiden können als rein okuläres Problem, aber auch im Rahmen einer potenziell letalen Grunderkrankung auftreten. Diagnosestellung und Management dieser Erkrankung sind eine große Herausforderung für den Augenarzt. Neben therapeutischen Grundprinzipien für alle nicht infektiösen Keratitiden und Ulzerationen bestimmt die jeweilige Pathogenese die spezifische, u. U. lebensrettende Behandlung. Daher muss vor jeder Therapie eine akkurate, wegweisende Diagnose stehen.

Purpose: To evaluate the relationship between signs and symptoms of dry eye disease (DED) in a clinic-based population. Methods: In a retrospective analysis, clinical signs and symptoms were evaluated for 344 subjects (n = 82, normal; n = 263, dry eye), across 11 sites from the EU and United States. Pearson correlations between signs and symptoms (r2) and an independent components analysis (ICA) mixing matrix were derived from the data set. Similar analysis was performed on an independent data set from 200 subjects in a previous study in Munich, Germany. Results: No correlations above r2 = 0.17 were found between any signs and symptoms, except for corneal and conjunctival staining, which reported an r2 = 0.36. In the multisite study, the average r2 for osmolarity (0.07), tear breakup time (0.12), Schirmer test (0.09), corneal (0.16) and conjunctival staining (0.17), meibomian grading (0.11) and Ocular Surface Disease Index® (0.11) were consistently low. Among patients who showed evidence of DED by consensus of clinical signs, only 57% reported symptoms consistent with a diagnosis of DED. Similar results were observed in the Munich-based study data set. Each component of the ICA mixing matrix exhibited minimal residual information. Conclusions: No consistent relationship was found between common signs and symptoms of DED. Each type of measurement provides distinct information about the condition of the ocular surface. These results also demonstrate that symptoms alone are insufficient for the diagnosis and management of DED and argue for a consensus of clinical signs that better reflect all aspects of the disease.

Die Inzidenz eines Makulaforamens am Partnerauge bei Patienten mit Makulaforamen Stadium I – IV nach Gass wird in 3 – 14% beobachtet. Uber die Entwicklung eines Makulaforamens in einem Zeitraum von 19 – 54 Monaten gibt es extrem unterschiedliche Angaben zur Haufigkeit zwischen 1 und 22%. Nach klinischem Eindruck besteht jedoch eine weit hohere Zahl an Veranderungen der vitreomakularen Grenzflache am meist asymptomatischen zweiten Auge bereits bei Erstvorstellung in einer Klinik. Wir untersuchten retrospektiv 88 Patienten, die sich zwischen Januar und Oktober 1994 mit einem Makulaforamen vorstellten. Wir gingen der Frage nach, wie haufig am Partnerauge ein Makulaforamen bzw. ein Macular pucker besteht, da vieles auf gemeinsame pathogenetische Faktoren dieser beiden Veranderungen der vitreoretinalen Grenzflache hinweist. Wir untersuchten auserdem, wie sich Anzahl und Form der Makulaveranderungen des Partnerauges in Patienten unterscheiden, deren Makulaforamen am ersten Auge operiert wurde und Patienten, deren erstes Auge abwartend beobachtet wurde. In der Gruppe der Patienten, die operiert worden waren, fand sich ein Makulaforamen Stadium I und II in je 8% und ein Makulaforamen Stadium III/IV in 6% der Patienten am Partnerauge. Bei Patienten der Beobachtungsgruppe bestanden lediglich Fruhstadien von Makulaforamina in 18% der Falle. Insgesamt zeigte sich bei Erstvorstellung bei 21% der Patienten mit Makulaforamen ebenfalls ein Makulaforamen in 7% ein Macular pucker am Partnerauge. Somit war die Inzidenz pathologischer Veranderungen an der vitreomakularen Grenzflache in 28% der Partneraugen weit haufiger als in der Literatur beschrieben. Die Tatsache, das sowohl Fruhformen von Makulaforamina als auch Macular pucker gefunden wurden, unterstreicht klinisch die These pathogenetischer Gemeinsamkeiten von Makulaforamina und Macular pucker. Da in dieser Studie lediglich die Inzidenz pathologischer Veranderungen erfast wurde, ist mit einer weit hoheren Zahl an sich entwickelnden Makulaforamina und Macular pucker am Partnerauge bei Makulaforamen im zeitlichen Verlauf zu rechnen.

Eine in bisher wenigen Arbeiten erwahnte Operationstechnik in der Behandlung durchgreifender Makulaforamina besteht neben der Entfernung des Glaskorpers und der Glaskorperrinde in dem Erkennen und Entfernen einer Membran an der vitreoretinalen Grenzflache. Die funktionellen und anatomischen Ergebnisse dieser Technik werden in dieser retrospektiven Studie an 42 Patienten vorgestellt. Patienten und Methode: Makulaforamina im Stadium II sowie im Stadium III/IV nach Gass zeigten jeweils 21 Patienten. Das operative Vorgehen bestand in der Pars-plana-Vitrektomie, der Entfernung einer – wenn vorhanden – vitreoretinalen Grenzmembran und einer 15%-C2F6- bzw. 20%-SF6-Gastamponade. Der Nachbeobachtungszeitraum betrug mindestens 6 Monate. Ergebnisse: Sechs Monate postoperativ zeigten 53% der Gesamtgruppe eine Visusverbesserung, 26% keine Veranderung und 21% eine Visusverschlechterung. In der Untergruppe, in der eine vitreoretinale Grenzmembran entfernt werden konnte, (31 Patienten), kam es bei 68% zu einer Visusverbesserung, bei 26% blieb der Visus gleich und in einem Fall zeigte sich eine Verschlechterung. Ein anliegendes Makulaforamen konnte in 80% gefunden werden; 90% klagten praoperativ uber Metamorphopsien. In der Untergruppe, in der es zu keiner Entfernung der vitreoretinalen Grenzmembran kam (11 Patienten), zeigte kein Patient eine Visusverbesserung, bei 27% blieb der Visus gleich und bei 73% kam es zu einer Verschlechterung. Bei 27% konnte 6 Monate postoperativ ein anliegendes Makulaforamen gefunden werden; 36% gaben praoperativ Metamorphopsien an. Schlusfolgerung: Eine konsequente Entfernung einer vitreoretinalen Grenzmembran verbessert die Visusprognose, fuhrt haufiger zu einer Wiederanlage des Makulaforamens und reduziert Metamorphopsien. Nach unseren Ergebnissen scheint es Makulaforamen mit unterschiedlicher Pathogenese zu geben, die ein unterschiedliches operatives Vorgehen erfordern und zu verschiedenen klinischen Erfolgen fuhren.

Purpose: To compare the occurrence of malignancy in patients with severe ocular inflammatory disease treated with systemic corticosteroids alone or with systemic immunosuppressive drugs with or without systemic corticosteroids. Methods: The clinical records of 543 patients with ocular inflammatory disease treated with systemic corticosteroids and/or immunosuppressive chemotherapy were reviewed in a retrospective cohort study. Characteristics of patients treated with corticosteroids alone were compared with characteristics of patients treated with immunosuppressive agents with or without preceding corticosteroid treatment. The rates of malignancy after initiation of drug therapy were compared using an exact test for incidence rate data. Results: Compared with patients treated with corticosteroids alone, patients treated with immunosuppressants with or without corticosteroid treatment were older and had more severe systemic disease. During a total of 1261 person-years of follow-up, a malignancy developed in five patients. The rate of malignancy in the immunosuppressant group (4 malignancies during 968 person-years of follow-up) was not significantly different from the rate in the corticosteroids alone group (1 malignancy during 293 person-years of follow-up) ( P >0.90, exact test for incidence rate data). Conclusion: These findings do not support the hypothesis of an increased risk of malignancy in patients with severe ocular inflammatory disease who are treated with systemic immunosuppressive agents compared with patients treated with systemic corticosteroids.

Purpose: To describe the distribution of basement membrane zone (BMZ) components in normal conjunctiva, conjunctiva of patients with glaucoma and normal skin. Methods: Thirty-five normal conjunctival biopsies and 16 conjunctival biopsies of patients with glaucoma under topical anti-glaucomatous therapy were examined by immunohistochemistry. Antibodies were directed against laminin a chains, laminin subchains a1, a2, a3, b1, b3, c1, c2, c3, kalinin, b4-integrin, and collagens IV and VII. Results were compared to the antigen distribution at the BMZ in normal skin. Results: The BMZ of skin stained positive for all antibodies tested. In contrast to skin, the BMZ of normal conjunctiva was negative for laminin subunits a2, b1, b3, c 2a ndc3 in most or all specimens. Positive findings at the conjunctival BMZ of patients with glaucoma were comparable to normal conjunctiva for laminin a, a1, b3, c1, c3, laminin 5, b4-integrin, collagen IV and collagen VII. However, staining of the BMZ with antibodies to laminin b1 (p = 0.002) and c2 (p = 0.017) was seen in a significantly higher rate in glaucoma compared to controls. Conclusion: Characteristic differences exist in the antigenicity of the BMZ in normal skin, normal conjunctiva and conjunctiva from patients with glaucoma, especially for laminin subchains. These differences may explain the variable ocular involvement in diseases of the BMZ. Moreover, they may explain the susceptibility of patients with glaucoma to develop mucous membrane pemphigoid-like disease. Alterations in conjunctival BMZ in glaucoma may be induced by longterm topical anti-glaucoma medications including various preservation agents.

Natural killer (NK) cells and acquired cell-mediated immunity effector cells (delayed type hypersensitivity (DTH) and cytotoxic T lymphocytes (CTL)) have been reported to play a vital role in the defence of the host against tumour and viral infections in locations other than the eye. A vigorous cellular inflammatory response to viral infections of the cornea, however, with the attendant damage to the corneal clarity, has obvious evolutionary disadvantages, and a substantial body of evidence indicates that in animals (e.g. mice) which are highly susceptible to inflammatory destruction of the cornea following corneal encounter with herpes simplex virus, it is the animal's immunological/inflammatory response which is responsible for the corneal damage. We examined the role of natural killer cells in the development of herpes stromal keratitis (HSK) in NK-deficient (C57BL/6J-bgj (beige)) mice and their NK-competent (C57BL/6J (black) relatives. The beige (NK-deficient) mice were just as resistant to HSK as were the black mice. We also studied the effects of NK cell depletion of BALB/c Igh-1 disparate congenic mice. C.AL-20 (Igh-1d) mice are ordinarily highly susceptible to necrotising HSK. In vivo NK-cell depletion in these mice significantly decreased the incidence and severity of HSK in these animals (p < 0.0005). Corneas from untreated C.AL-20 mice contained T cells, macrophages and NK cells. The corneal infiltrate from NK-depleted C.AL-20 mice consisted of T cells and macrophages but no NK cells. These data indicate that NK cells are participants in the development of HSK in the murine model of this disease.

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) function in the remodelling of the extracellular matrix in morphogenesis, angiogenesis, tissue repair, and tumor invasion. Elevated levels of distinct MMPs in tumor tissue are related to worse prognosis. However, no overall consistent pattern of expression in human cancer has been identified. The aim of the present study was to evaluate the expression of MMP-1, -9, -13 and TIMP-1 in tumor epithelial cells and surrounding connective tissue in primary basal cell carcinomas (BCC) of the eyelid, and to assess their role as prognostic markers for tumor recurrence.Surgical specimens of 49 histologically proven primary BBCs of the eyelid of different histological subtypes were included. Immunohistological studies were performed using antibodies against MMP-1, MMP-9, MMP-13 and TIMP-1, and staining intensity was analyzed semi-quantitatively.MMP-1, -9, -13, and TIMP-1 were expressed at various intensities in epithelial tumor cells and surrounding stromal cells including fibroblasts, inflammatory cells, and vascular endothelial cells in all tumor subtypes. Staining was especially prominent at the invading edge of the BCC. A statistically significant correlation was seen between increased TIMP-1 expression in tumor and/or stromal cells with the presence of MMP-13 (p = 0.007 and p 0.0001 respectively). Moreover, TIMP-1 expression in tumor and/or stroma was significantly associated with relapse (p = 0.012 and p = 0.042 respectively).MMP-9, MMP-13 and TIMP-1 expression may serve as a prognostic marker for early tumor invasiveness. Moreover, up-regulation of TIMP-1 in tumor and/or surrounding stromal cells may indicate an increased risk for BCC recurrence.

Aim—To prospectively evaluate peripheral visual fields after vitrectomy for idiopathic macular holes. Methods—Goldmann perimetry was performed in 105 patients before, as well as 6 weeks and 12 months after macular hole surgery. Results—Only one patient (

Hyperosmolarity of the tear film is recognized as an important pathogenetic factor in dry eye syndrome (DES). Hyperosmolarity testing has been hampered in the past by difficulties in tear collection and analytic procedures that required laboratory facilities. The Tearlab Osmolarity System is a new user-friendly tool that only needs tiny volumes for analysis and determines hyperosmolarity semi-automatically. We measured tear film osmolarity with the Tearlab in 200 healthy individuals and patients with DES. Dry eye diagnosis was established whenor =3 of the following criteria were fulfilled:(1) Ocular Surface Disease Index15; (2) staining of the cornea in the typical interpalpebral area; (3) staining of the conjunctiva in the typical interpalpebral area; (4) tear film break-up time7 s; (5) Schirmer test7 mm in 5 min; (6) the presence of blepharitis or meibomitis. Tear film osmolarity, as measured by Tearlab, did not show any correlation with the 6 clinical signs of dry eye. Moreover, tear film osmolarity testing could not discriminate between patients with DES (308.9 +/- 14.0 mosm/l) and the control group (307.1 +/- 11.3 mosml/l). Tear film osmolarity did not correlate to artificial tear use. Technical problems with the Tearlab, reflex tearing, or the difficulty in establishing a dry eye diagnosis with the recommended tests may account for these results. Further investigations are necessary before recommending this tool for daily clinical practice.

Hyperosmolarity of the tear film is recognized as an important pathogenetic factor in dry eye syndrome (DES). Hyperosmolarity testing has been hampered in the past by difficulties in tear collection and analytic procedures that required laboratory facilities. The Tearlab Osmolarity System is a new user-friendly tool that only needs tiny volumes for analysis and determines hyperosmolarity semi-automatically. We measured tear film osmolarity with the Tearlab in 200 healthy individuals and patients with DES. Dry eye diagnosis was established when > or =3 of the following criteria were fulfilled:(1) Ocular Surface Disease Index > 15; (2) staining of the cornea in the typical interpalpebral area; (3) staining of the conjunctiva in the typical interpalpebral area; (4) tear film break-up time < 7 s; (5) Schirmer test < 7 mm in 5 min; (6) the presence of blepharitis or meibomitis. Tear film osmolarity, as measured by Tearlab, did not show any correlation with the 6 clinical signs of dry eye. Moreover, tear film osmolarity testing could not discriminate between patients with DES (308.9 +/- 14.0 mosm/l) and the control group (307.1 +/- 11.3 mosml/l). Tear film osmolarity did not correlate to artificial tear use. Technical problems with the Tearlab, reflex tearing, or the difficulty in establishing a dry eye diagnosis with the recommended tests may account for these results. Further investigations are necessary before recommending this tool for daily clinical practice.

We present a case of a dislocated posterior lamellar lenticule into the vitreous cavity during Descemet stripping automated endothelial keratoplasty. After insertion of the donor disc in a partially vitrectomized eye with partial iris loss, the graft dislocated into the vitreous cavity. With a standard 3-port vitrectomy and the help of perflourocarbon fluid, the graft was lifted into the anterior segment of the eye and firmly attached to the recipient cornea using liquid-air exchange. The postoperative follow-up was without complications. The cornea was clear at the third day after surgery without recurrent graft dislocation.

■ In vivo confocal microscopy allows the visualization of the ocular surface at the cellular level

The human gland of Moll located at the margin of the eyelids is a specialized apocrine gland, the function of which is not exactly known. The presence of antimicrobial proteins was identified in this gland recently, suggesting a function in the external ocular defense barrier against pathogens. In this study, we have demonstrated beta-defensin-1, beta-defensin-2 and cathelicidin (LL-37) in the secretory endpieces of the glands of Moll using immunohistochemical methods. beta-Defensin-1, beta-defensin-2 and cathelicidin (LL-37) showed a weak to moderately intensive staining pattern. The strongest immunolocalization of beta-defensin-1 was observed in the apical protrusions of the gland, which could also be observed but to a lesser extent in the case of beta-defensin-2 and cathelicidin. In active glandular cells, a granular staining pattern could be observed. beta-Defensin-1 and beta-defensin-2 varied in staining intensities, and even within one section strongly and weakly stained cells can coexist side by side. Also cells that, according to morphological criteria, appeared to be inactive still had an apical beta-defensin-1 immunolabeling. We assume that beta-defensin-1, beta-defensin-2 and cathelicidin (LL-37) work together with other antimicrobial peptides and proteins to create a defensive barrier against microbial invasion at the ocular surface.

To analyze the appearance of normal conjunctiva and conjunctival inflammation by in vivo confocal microscopy.Conjunctiva of 15 normal patients and 21 patients with conjunctivitis including bacterial, papillary, follicular, granulomatous, and cicatrizing disease were analyzed by the Heidelberg retina tomograph (HRTII)/Rostock cornea modul (RCM).Scans of normal bulbar and tarsal conjunctiva corresponded well to the established anatomy except for a prominent, thickened epithelial basement membrane observed by in vivo microscopy. Presumed goblet cells were visible throughout the conjunctival epithelium. Adenoid structures and hair follicles were discernible in the tarsal conjunctiva in vivo. Conjunctival perfusion could be observed directly. Acute and chronic inflammatory cells, conjunctival papillary, and follicular reactions, as well as conjunctival cicatrization, could be discriminated. In a patient with conjunctival granuloma, in vivo confocal microscopy disclosed suture material inside the lesion.Confocal microscopy using near-infrared laser light is a useful new tool in the analysis of conjunctival tissue in vivo. It is a valuable aid in the differential diagnosis of conjunctival inflammation and thus may guide therapeutical decisions.

To analyze filtering blebs after trabeculectomy by means of in vivo confocal microscopy and to correlate the images with clinical bleb appearance and function.In vivo confocal microscopy using the Heidelberg Retina Tomograph/Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany) was performed in 53 filtering blebs in 45 patients 6 days to 30 years postoperatively.In vivo confocal microscopic findings significantly correlated with good bleb function included the number of epithelial microcysts (P = .03), a large total stromal cyst area (P = .009), the absence of encapsulated stromal cysts (P = .002), minimal vascularization (P = .05), and the absence of tortuous conjunctival vessels (P = .01). In contrast, a hyperreflective condensed bleb stroma was significantly associated with bleb failure (P.001). Bleb stroma mainly consisting of a rarified collagenlike network was significantly linked to trabeculectomy performed with mitomycin C (P = .001). Epithelial and stromal inflammation were observed at a median of 1 and 4 months after surgery, respectively.In vivo confocal microscopy using the Heidelberg Retina Tomograph/Rostock Cornea Module permits diagnostic imaging of filtering blebs and differentiation between good and insufficient bleb function. Moreover, the postoperative inflammatory reaction can be monitored directly for adapted postoperative anti-inflammatory treatment.

Human secretoglobin (SCGB) 2A1 (or lipophilin C, lacryglobin, mammaglobin B) is a small protein of unknown function that forms heterodimers with secretoglobin 1D1 (lipophilin A) in tears. SCGB 2A1 is homologous to mammaglobin (mammaglobin A) and the C3 component of prostatein, the major secretory protein of the rat ventral prostate. Androgen-dependent expression of SCGB 2A1 has been observed in the prostate. Besides identification of SCGB 2A1 in the tear proteome only its mRNA had been detected in the lacrimal gland. Here, we report expression of SCGB 2A1 in all ocular glands and in the keratinized stratified squamous epithelium of the eyelid as well as in the stratified epithelium of the conjunctiva and in the orbicularis oculi muscle. Almost all of these tissues are also known to express the androgen receptor. Therefore, we conclude that presence of the androgen signalling machinery could be the main general determinant of SCGB 2A1 expression. Implications of the presence in tear fluid of an androgen-regulated secretoglobin, which most likely binds hydrophobic ligands, for tear film lipid layer formation and function is discussed.

Purpose: To report clinical, histologic, and electron microscopic findings in several consecutive keratoplasties with recurrent pancorneal calcification in a patient with chronic graft versus host disease and severe keratoconjunctivitis sicca following bone marrow transplantation for chronic myelogenous leukemia. Methods: Altogether 5 penetrating keratoplasties were performed in both eyes for descemetocele formation and corneal perforation as well as pancorneal calcification associated with severe visual loss. Histologic examination and electron microscopy were performed on the corneal buttons obtained. Results: Histology and electron microscopy confirmed pancorneal extracellular calcium deposition with increasing severity in each consecutive keratoplasty. Calcification was associated with necrosis and inflammation of the corneal stroma. Clinically unsuspected fungal keratitis was observed in 1 specimen. Conclusions: Keratoconjunctivitis sicca, epithelial defects, corneal inflammation, and infection are most probably responsible for the recurrent pancorneal calcification seen in our patient. The role of cytokines in this complication is discussed.

Keratitis-ichthyosis-deafness syndrome (KID; MIM 148210) is a rare congenital disorder characterized by vascularizing keratitis, sensorineural hearing loss (HL), and progressive erythrokeratoderma. Clinical variability including a fatal course of KID in the first year of life has been reported. Germline missense mutations in GJB2, encoding connexin-26, were recently found to cause KID in 14 unrelated juvenile and adult patients. We identified a de novo GJB2 mutation G45E in a patient displaying the fatal form of the disease. No mutations were detected in five other connexin and mitochondrial genes. The G45E mutation was not reported previously in Caucasian patients but was the third most common GJB2 mutation (16% of disease alleles) in Japanese patients with autosomal recessive non-syndromic HL. This finding suggests different modes of action of the same GJB2 mutation depending on the genetic background. This hypothesis was further substantiated by our observation of a variable clinical course in unrelated KID patients from Austria harboring the common D50N mutation in GJB2.

Since the 1980s, combined perforating keratoplasty and extracapsular cataract surgery with intraocular lens implantation (triple procedure) has been performed with increasing success for patients with corneal disease and cataract. Advantages include prompt visual rehabilitation, protection of the transplanted endothelium from sequential cataract surgery, and similar up to superior functional results following triple procedures. In the following review article, the authors discuss advantages and disadvantages of triple procedures, alternative surgical techniques, problems in intraocular lens power calculation, intraoperative pitfalls, and postoperative results of combined keratoplasty, cataract removal, and intraocular lens implantation.

Vielfaltige Verbindungen bestehen zwischen der Haut und dem Sehorgan, und eine Vielzahl von Hauterkrankungen geht mehr oder minder haufig mit einer okularen Beteiligung einher. In Tabelle 1 sind die aus ophthalmologischer Sicht wichtigsten Beispiele dermatologischer Erkrankungen zusammengefasst, die zu klinisch bedeutsamen Augenveranderungen fuhren. Nicht selten, vor allem in abortiven oder atypischen Fallen, ist die ophthalmologische Untersuchung richtungsweisend und in der Lage, die dermatologische Diagnose zu sichern.

PURPOSE: Recurrent or persistent corneal erosions and ulcerations are typical complications of atopic keratoconjunctivitis. Toxic eosinophil granule proteins such as major basic protein (MBP) and eosinophil cationic protein (ECP) may be involved in this pathogenetic process. This study was designed to demonstrate the presence of toxic eosinophil granule proteins in corneal tissue from a patient with corneal complications of atopic keratoconjunctivitis. DESIGN: Observational case report. METHODS: Three corneal buttons of a patient with atopic keratoconjunctivitis associated ulcerations or scarring were examined by light microscopy and by immunofluorescence technique. RESULTS: A linear deposition of eosinophil granular substance was detected subepithelially above Bowman’s membrane in all corneal buttons. Indirect immunofluorescence identified this material as MBP and ECP. The deposits were not limited to the area of ulceration, but were also found underneath intact corneal epithelium. Multiple eosinophils were present in the upper corneal stroma. Normal corneas and negative control sections of the pathologic buttons revealed only minimal nonspecific staining at the surface of the epithelium. CONCLUSIONS: Both MBP and ECP are known to affect human corneal epithelial cell viability and morphology in vitro. Moreover, MBP was shown to inhibit epithelial migration and protein synthesis. These toxic eosinophil proteins may also be responsible for corneal instability, recurrent and persistent corneal epithelial defects and ulcerations in patients with atopic keratoconjunctivitis.

Background Although bullous pemphigoid (BP) is the most frequent autoimmune bullous disease and is associated with a considerable case-fatality rate, little is known about factors that influence its prognosis. Objective To identify prognostic factors for lethal outcome in the first year after the initial hospitalization in patients with BP. Design A multicenter retrospective cohort study. Setting Seven dermatologic university hospitals in Germany. Participants A total of 369 patients diagnosed as having BP between January 1, 1987, and December 31, 1997. Statistics Univariate (Kaplan-Meier) and multivariate (Cox regression) analysis. Results Of the 369 patients with BP, 209 (57%) died, 106 (29%) within the first year after hospitalization. Fifty-four percent were women. The mean ± SD age at entry was 77.3 ± 11.1 years. The patients with BP were followed up to 10.5 years, with a median time of 1.8 years to death or interview (25th and 75th quartiles, 0.5 and 4.0 years). The major risk factors for lethal outcome in the first year after hospitalization were an increased age, with a multivariate risk estimate of 3.2 (95% confidence interval [CI], 1.9-5.2) for age greater than 80.4 years (median); a daily glucocorticosteroid dosage of more than 37 mg (75th quartile) at discharge, with a multivariate risk estimate of 2.5 (95% CI, 1.5-4.3); serum albumin levels of 3.6 g/dL or less (25th quartile), with a multivariate risk estimate of 2.6 (95% CI, 1.5-4.4); and an erythrocyte sedimentation rate greater than 30 mm/h (75th quartile), with a multivariate risk estimate of 1.7 (95% CI, 1.1-2.8). Conclusions There is a considerable case-fatality rate in patients with BP. Older patients who require a higher dosage of oral glucocorticosteroids at hospital discharge and who have low serum albumin levels are at greater risk of death within the first year after hospitalization. These prognostic factors should be considered in the care of patients with BP as well as in the design of future clinical trials.

PURPOSE: To demonstrate whether indocyanine green stains the inner limiting membrane of the retina or residual vitreous cortex. METHODS: We report on the intraoperative staining patterns of the vitreomacular interface in 10 eyes of 10 consecutive patients who underwent vitrectomy with indocyanine green staining for macular hole formation and diffuse diabetic macular edema. RESULTS: In five eyes of five patients with macular holes, indocyanine green staining of the macula after posterior vitreous detachment resulted in an immediate visibility of a discernable membrane that was not previously seen. In five eyes of five patients with diffuse diabetic macular edema and adherent cortical vitreous, indocyanine green failed to stain the vitreomacular interface. After peeling off the residual vitreous cortex, however, a discernable membrane could be identified using indocyanine green dye again. Light and transmission electron microscopy revealed the inner limiting membrane as the membrane that had been stained and removed in all specimens. CONCLUSION: Indocyanine green selectively stains the inner limiting membrane. Staining of the vitreomacular interface using indocyanine green as a vital dye enables the surgeon to distinguish between the residual vitreous cortex and the inner limiting membrane, and it allows safer and easier removal of the inner limiting membrane.

Ocular leprosy is rarely seen in developed countries. We report the long-term follow-up of a patient with bilateral uveitis, glaucoma, and keratitis. Skin, iris and aqueous humor biopsies disclosed abundant Wade-Fite-positive organisms consistent with Mycobacterium leprae. Leprosy must be considered in the differential diagnosis of keratitis and uveitis.

· Background: The role of tangential traction exerted by epiretinal membranes in the pathogenesis of macular holes is not fully understood. Furthermore, the role of glial cells in the formation and/or closure of macular holes remains to be elucidated. · Methods: To better understand the pathogenesis of macular hole formation and to compare the ultrastructural features of epiretinal membranes associated with macular holes of primary and secondary etiology, we harvested 23 translucent epiretinal membranes associated with macular holes stages III—IV at the time of pars plana vitrectomy and examined them electron microscopically. Eighteen membranes were obtained from patients with idiopathic macular holes, 3 membranes from patients with myopic macular holes and 2 epiretinal membranes were associated with macular holes which had developed after retinal detachment surgery. · Results: Eighteen membranes contained a continuous undulating piece of inner limiting lamina (ILL). Sixteen of 18 epiretinal membranes at the margins of idiopathic macular holes, 2 of 3 membranes in myopic macular holes and both membranes associated with a macular hole after retinal detachment surgery demonstrated mono- or multilayers of fibrous astrocytes with single macrophage- or fibrocyte-like cells. Vitreous and newly formed collagen occupied the space between the ILL and the glial cells. Three macular holes were surrounded by rather firmly attached acellular ILL. · Conclusion: Glial cells and newly formed collagen may play an important role in macular hole formation by exerting tangential traction regardless of the underlying disease process. Glial cells, however, may also be involved in healing of the retinal defect and pars plana vitrectomy with peeling of an epiretinal membrane, and/or the ILL may induce directed glial cell proliferation and migration. The similar ultrastructure of epiretinal membranes associated with macular holes and “simple epiretinal membranes” as described by Foos [8] suggests a common pathogenesis for macular holes and macular pucker.