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BACKGROUND Dry eye disease (DED) is a common disorder, accounting for up to 35% of the general population. Therefore, we hypothesized that laryngopharyngeal reflux (LPR), inducing refluxate rising into airways, may involve the ocular surface and may either induce or worsen DED. AIM To investigate the prevalence and relevance of suspected LPR in DED patients and subjects with refractive problems (RP) without DED, they were defined as non-dry eye group (NEG) in clinical practice. METHODS This retrospective study included consecutive patients evaluated because of dry eye-like symptoms at eight tertiary ophthalmological clinics. Parameters included reflux symptom index (RSI), ocular surface disease index (OSDI), symptom assessment in dry eye (SANDE) for frequency and severity, Schirmer test, tear break-up time (BUT), and Oxford grading. RESULTS The study included 245 subjects (72.5% females; mean age 56.3 years), 152 DED patients, and 93 sex- and age-matched NEG subjects. Pathological RSI (score>13) was detected in 80 subjects (32.6%); 68 (85%) with DED and 12 (15%) CG (OR = 8; p

Hornhautveranderungen bei Liderkrankungen sind haufig und konnen den Krankheitsverlauf erheblich komplizieren. Sie konnen sich als Refraktionsanomalien, Hornhautdegenerationen, Erkrankungen der Augenoberflache, Hornhautinfiltrate, Hornhautvaskularisationen und Hornhautulzerationen bis hin zur Hornhautperforation manifestieren. Pathophysiologisch sind Druckkrafte, Exposition, Trichiasis und Distichiasis, Augenreiben, Entzundung und Infektion bedeutsam. Eine Vielzahl von Liderkrankungen geht mit Erkrankungen der Hornhaut einher wie Lidfehlstellungen, Lidtumoren, Lidinfektionen, die allergische Liddermatitis und Blepharitis, Meibomitis oder Meibom-Drusen-Dysfunktion.

Die neurotrophe Keratopathie ist gekennzeichnet durch Hornhautoberflachenveranderungen, persistierende Epitheldefekte und/oder Hornhautulzerationen im Rahmen einer Hornhautsensibilitatsstorung. Aufgrund des variablen Erscheinungsbildes wird die neurotrophe Keratopathie oft ubersehen oder zu spat im Krankheitsverlauf diagnostiziert. Ziele sind eine Darstellung der Klinik sowie Empfehlungen zur korrekten Diagnose. Es erfolgen eine Analyse der vorhandenen Literatur und eine Diskussion von aktuellen Grundlagenarbeiten zum Thema. Die neurotrophe Keratopathie geht definitionsgemas mit Veranderungen der Hornhautnerven einher, die zur Beeintrachtigung von sensorischen und trophischen Funktionen mit konsekutivem Zusammenbruch des Hornhautepithels und Storungen in Tranenfilm, Hornhautepithel und -stroma fuhren. Sie kann im Rahmen von Infektionen, Autoimmunerkrankungen, nach Trauma und okularer Chirurgie, bei intrakraniellen Neoplasien, bei Systemerkrankungen und genetischen Syndromen auftreten. Sie wird in 3 Stadien eingeteilt: mild (Epithelveranderungen ohne Epitheldefekt), moderat (Epitheldefekt) und schwer (Stromabeteiligung). Wichtigstes klinisches Zeichen ist die reduzierte oder fehlende Hornhautsensibilitat. Daher ist die Testung der Hornhautsensibilitat neben Anamnese, klinischer Untersuchung und Zusatzuntersuchungen wie Vitalfarbung und, wenn moglich, konfokaler In-vivo-Mikroskopie unerlasslich zur Diagnose der Erkrankung. Die korrekte Diagnose und Klassifikation der neurotrophen Keratopathie ermoglichen eine stadiengerechte Stufentherapie der Erkrankung sowie die Reduktion von Progression und Komplikationen.

International audience; The pathophysiology of glaucoma is complex, multifactorial and not completely understood. Elevated intraocular pressure (IOP) and/or impaired retinal blood flow may cause initial optic nerve damage. In addition, age-related oxidative stress in the retina concurrently with chronic mechanical and vascular stress is crucial for the initiation of retinal neurodegeneration. Oxidative stress is closely related to cell senescence, mitochondrial dysfunction, excitotoxicity, and neuroinflammation, which are involved in glaucoma progression. Accumulating evidence from animal glaucoma models and from human ocular samples suggests a dysfunction of the para-inflammation in the retinal ganglion cell layer and the optic nerve head. Moreover, quite similar mechanisms in the anterior chamber could explain the trabecular meshwork dysfunction and the elevated IOP in primary open-angle glaucoma. On the other hand, ocular surface disease due to topical interventions is the most prominent and visible consequence of inflammation in glaucoma, with a negative impact on filtering surgery failure, topical treatment efficacy, and possibly on inflammation in the anterior segment. Consequently, glaucoma appears as an outstanding eye disease where inflammatory changes may be present to various extents and consequences along the eye structure, from the ocular surface to the posterior segment, and the visual pathway. Here we reviewed the inflammatory processes in all ocular structures in glaucoma from the back to the front of the eye and beyond. Our approach was to explain how para-inflammation is necessary to maintain homoeostasis, and to describe abnormal inflammatory findings observed in glaucomatous patients or in animal glaucoma models, supporting the hypothesis of a dysregulation of the inflammatory balance toward a pro-inflammatory phenotype. Possible anti-inflammatory therapeutic approaches in glaucoma are also discussed.

A cystic lesion of the lid margin was excised suspecting basal cell carcinoma. On histology, black-turquoise pigment was seen in the dermis adjacent to the basal cell carcinoma. It was pronounced perivascular, intracellular in macrophages and fibroblasts, but also extracellular as free pigment in the tissue, compatible with an eyelid line tattoo. Typical tissue reactions to tattoo ink, meibomian gland dysfunction after lid margin tattoo, as well as inflammatory reactions in the retina and choroid associated with tattoos distant from the eye are discussed. The correlation of lid tumors and lid margin tattoos seems coincidental.

Purpose: Meibomian gland disease is generally accepted as the leading cause for evaporative dry eye disease (DED). In a previous study, perfluorohexyloctane, a semifluorinated alkane, has been demonstrated to significantly increase tear film breakup time and to reduce corneal fluorescein staining in patients with evaporative DED, thereby vastly reducing dry eye-related symptoms. This study was set up to evaluate perfluorohexyloctane in a larger population of patients with Meibomian gland dysfunction. Methods: Seventy-two patients with Meibomian gland disease and associated dry eye received 1 drop of perfluorohexyloctane 4 times daily during an observational, prospective, multicenter, 6–8-week study. Clinical assessment included best-corrected visual acuity, intraocular pressure, Schirmer test I, tear film breakup time, anterior and posterior blepharitis assessment, number of expressible Meibomian glands, meibum quality and quantity, ocular surface fluorescein staining, lid margin and symptom assessment, and Ocular Surface Disease Index (OSDI©). Results: From the 72 patients recruited, 61 completed the trial per protocol. Nine patients did not apply the medication as recommended and 2 patients were lost to follow-up. Tear film breakup time, corneal and conjunctival fluorescein staining, number of expressible Meibomian glands, and severity of anterior and posterior blepharitis significantly improved after 6–8 weeks of perfluorohexyloctane application. In addition, symptoms improved as demonstrated by a significant decrease of OSDI-values from 37 (±13) to 26 (±16). Conclusions: In concordance with previous findings, 6–8 weeks of topical application of perfluorohexyloctane significantly improves clinical signs of Meibomian gland disease and associated mild to moderate DED.

Purpose To investigate histopathologic, immunohistochemical, and electron microscopic findings in 8 keratoplasty specimens with a history of corneal collagen crosslinking (CXL) for keratoconus. Five new (hitherto unreported) and 3 previously published specimens were analyzed. Methods Corneal buttons of 8 keratoconus corneas (5-114 months after CXL) were compared with 5 keratoconus specimens without CXL and 5 normal corneas for morphological alterations. Corneal buttons were evaluated by light microscopy and immunohistochemistry using antibodies against CD34, PGP 9.5, nestin, telomerase reverse transcriptase, and Ki67 as well as by transmission electron microscopy. Results Keratoconus corneas after CXL showed a significant keratocyte loss (except 1 specimen with an increased keratocyte number), whereas keratoconus corneas without CXL revealed a higher keratocyte density compared with healthy controls. Keratocyte loss could be clinically correlated with corneal opacification and corneal perforation. In corneas after CXL, the remaining keratocytes appeared more polymorphic and revealed a different expression of surface markers similar to keratocytes in corneal scars. The presence of proteoglycans, nerves, and endothelial cells was unaffected by CXL. Conclusions CXL may cause permanent keratocyte loss or repopulation of altered keratocytes, resulting in clinical complications such as corneal opacification or perforation. Despite its good safety profile and high effectiveness in progressive keratoconus, CXL should be performed in accordance with current guidelines strictly adhering to protocol and safety standards.

Background/aimTo assess the treatment effect of 0.1% ciclosporin A cationic emulsion (CsA CE) versus vehicle on signs/symptoms of dry eye disease (DED) in various subgroups (moderate-to-severe DED/severe DED/Sjögren’s syndrome (SS)/SS with severe DED).MethodsPooled data were analysed from two similar phase III studies: SICCANOVE (moderate-to-severe DED) and SANSIKA (severe DED with severe keratitis). In both studies, patients aged ≥18 years received CsA CE 0.1% (n=395) or vehicle (n=339) once daily for 6 months. A composite responder efficacy endpoint (corneal fluorescein staining–Ocular Surface Disease Index (CFS–OSDI) at month 6) was used to evaluate the efficacy of CsA CE in alleviating signs/symptoms of DED (response defined as improvement of ≥2 grades in CFS and ≥30% in OSDI (baseline to month 6)). Human leucocyte antigen-DR (HLA-DR) conjunctival expression was used as a biomarker of ocular surface inflammation.ResultsCsA CE–treated patients were significantly more likely to be CFS–OSDI responders than vehicle-treated patients in the overall (OR 1.66, 95% CI 1.11 to 2.50; P=0.015), severe DED (1.80, 1.04 to 3.19; P=0.038) and SS with severe DED (3.37, 1.20 to 11.19; P=0.030) populations. The difference was not significant for CsA CE versus vehicle for the overall Sjögren’s population (OR 1.77, CI 0.89 to 3.66; P=0.109). CsA CE also significantly reduced median HLA-DR expression versus vehicle at 6 months (P=0.002).ConclusionPooled phase III data indicate CsA CE produced significant improvement in signs/symptoms versus vehicle in patients with moderate-to-severe DED (especially in those with severe keratitis), including patients with SS with severe DED.

Background/aimsTo assess epidemiological tumour features, risk factors, clinical management and outcome of eyelid squamous cell carcinoma (SCC) and changes thereof. Furthermore, we searched for validating predictors of the American Joint Committee on Cancer (AJCC) 8 classification system.MethodsWe evaluated data of 117 patients with histologically proven eyelid SCC at a large tertiary German university centre between January 2009 and March 2020. This retrospective, monocentric analysis included descriptive statistics and non-parametric tests (pResultsHistologically controlled excision and follow-up was performed in 88 (75.2%) patients. In the remaining patients with higher T-category, individual adjuvant therapy combinations were initiated. We found higher numbers of nodal metastasis and recurrence for male patients and higher T-category (p=0.035, p=0.008 and p=0.001, pConclusionSpecial attention should be paid to male patients, tumour location in the upper medial eyelid and lymph node diagnostics. Prediction of DSS proved superior as per the AJCC 8 staging system.

Histopathological evaluation of ocular tissues is important in differentiating between infectious and autoimmune disease. Inflammation, necrosis and keratolysis are common to most forms of keratitis. Histopathology can be of great help in identifying the causative organism, establishing a final diagnosis and/or managing the patient with herpes simplex virus keratitis, mycotic keratitis, acanthamoeba keratitis or microsporidia keratoconjunctivitis. Important pathogenetic knowledge with therapeutic relevance has been gained from histopathological studies in nummular keratitis after epidemic keratoconjunctivitis and atopic keratoconjunctivitis.

Purpose We present an interesting case of a 26-year-old woman who underwent penetrating keratoplasty due to complete corneal scarring on the right eye after complicated myopic SMILE. Observations The spherical equivalent before laser treatment was −4.38D on the right eye and −4.00D on the left eye and topography showed a with-the-rule astigmatism on both eyes. The documented laser procedure was uneventful but wrong separation of the lenticule made a complete extraction of the lenticule not possible. The postoperative spherical equivalent showed −4,125D with an irregular astigmatism due to corneal scarring throughout the complete corneal stroma documented in OCT measurements. Due to serious anatomical changes of the cornea an uneventful penetrating keratoplasty was performed. Conclusion and importance SMILE procedure should be carefully performed as especially the lenticule separation and extraction can be a surgical challenge. In doubt, separation of the lenticule should not be enforced as it may lead to devastating outcome as presented in this case.

Background and purpose In September 2011 the cornea section of the German Ophthalmological Society (DOG) established the first German Acanthamoeba keratitis registry. The data of this multicenter survey are being collected, compiled and evaluated at the Department of Ophthalmology at the Saarland University. The aim of this article is to present an intermediate report. Patients and methods Data from 172 eyes with Acanthamoeba keratitis were collected during the last 10 years. For this interim report we actually evaluated 121 eyes (60.2 % female patients, average age 41.3 years) and collected the following data: date of onset of symptoms, date and method of diagnosis, initial diagnosis, anamnestic data, clinical symptoms and signs at diagnosis and during follow-up, conservative and surgical therapy. Criteria for inclusion in the Acanthamoeba registry was the established diagnosis of an Acanthamoeba keratitis with at least one of the methods described in this article. Results Acanthamoeba keratitis could be histologically proven in 55.3 % of the cases, via PCR in 25.6 %, with confocal microscopy in 20.4 % and using in vitro cultivation in 15.5 %. Clinical symptoms and signs in Acanthamoeba keratitis were pain in 67.0 %, ring infiltrates in 53.4 %, pseudodendritiform epitheliopathy in 11.7 % and keratoneuritis in 5.8 %. In 47.6 % of the cases the initial diagnosis was herpes simplex virus keratitis followed by bacterial keratitis in 25.2 % and fungal keratitis in 3.9 %. Acanthamoeba keratitis was the correct initial diagnosis in only 23.2 % of cases. The average time period between first symptoms and diagnosis was 2.8 ± 4.0 months (range 0-23 months). A triple therapy with Brolene® Lavasept® and antibiotic eye drops at least 5 ×/day was used in 54.5 % of eyes (n = 66). Penetrating keratoplasty was performed in 40.4 %, in 18 cases in combination with cryotherapy of the cornea. The mean graft diameter was 7.9 ± 1.1 mm (range 3.5-11.0 mm). The final visual acuity (Snellen visual acuity chart at 5 m) was comparable in the two groups of eyes with (5/40 ± 5/25) and without (5/32 ± 5/25) keratoplasty. Conclusion Acanthamoeba keratitis is a rare and often very late diagnosed disease and two thirds of the cases were initially misdiagnosed. The early recognition of the typical symptoms is crucial for the prognosis of the disease. All ophthalmological departments in Germany are invited to submit further data of all confirmed cases (berthold.seitz@uks.eu), whether retrospectively or prospectively in order to generate an adequate standardized diagnostic and therapeutic approach for this potentially devastating disease.

Purpose The aim of this study was to evaluate the outcome of penetrating keratoplasties, at the University Eye Hospital, Ludwig-Maximilians-University, Munich, Germany, using organ-cultured donor corneas and to identify preoperative risk factors, which may influence the event of graft failure. Methods In this study, 377 medical records of patients, who underwent penetrating keratoplasty between 2001 and 2011, were reviewed. Organ-cultured donor corneas were obtained from the eye bank, Ludwig-Maximilians-University, Munich, Germany. Donor-related and preoperative recipient-related risk factors for graft failure were analyzed by univariate and multivariate analyses. Results Graft failure occurred in 26% of patients. The following preoperative factors were significantly associated with graft failure by multivariate analyses: high donor age, low donor endothelial cell density, high patient age, indications of infectious keratitis, acute perforation of noninfectious keratitis, prior graft failure, chemical burn, trauma, glaucoma-associated corneal decompensation, high-risk graft indications, corneal edema, anterior chamber lens, diabetes mellitus, atopy, and autoimmune diseases. Conclusions This study demonstrated a success rate of 74%, which is consistent with previous studies. Various preoperative recipient-related factors seem to influence the outcome of penetrating keratoplasties, whereas few donor-related factors have a significant association with graft failure.

Purpose: To present light and electron microscopic as well as immunohistochemical findings after corneal cross-linking (CXL). Methods: Six keratoconus corneas after CXL, 12 keratoconus corneas without CXL, and 7 normal corneas were examined by light microscopy, indirect immunohistochemistry using antibodies against proapoptotic BAX, antiapoptotic survivin, and BCL-2, and anti-smooth muscle actin and, in part, by transmission electron microscopy. Direct immunofluorescence with 4'6-diamidino-2-phenylindole was performed to analyze keratocytes/area in the anterior, middle, posterior, peripheral, and central corneal stroma. Results: The period between CXL and keratoplasty ranged from 5 to 30 months. All keratoconus corneas showed the typical histological changes. Increased proapoptotic BAX expression and/or antiapoptotic survivin expression were noticed in keratocytes and endothelium in 2 keratoconus specimens after CXL. Smooth muscle actin was only observed in subepithelial scar tissue of 2 keratoconus corneas without CXL. Keratoconus corneas after CXL revealed a significant reduction in keratocyte counts in the entire cornea (P = 0.003) compared with keratoconus corneas without CXL and normal corneas. This difference was because of a loss of keratocytes in the anterior (P = 0.014) and middle (P = 0.024) corneal stroma. Keratocytes in CXL corneas were reduced in the center (P = 0.028) and the periphery (P = 0.047). Conclusions: CXL in human keratoconus can cause considerable morphologic corneal changes up to 30 months postoperatively. Especially noteworthy is a long-lasting, maybe permanent, keratocyte loss in the anterior and middle corneal stroma involving the central and peripheral cornea. As long-term corneal damage after CXL is of genuine concern, particular care should be taken to perform this procedure only in accordance with investigational protocols.

Dry eye disease (DED) is a common, multifactorial ocular condition with major impact on vision and quality of life. It is now well recognized that the pathophysiology of chronic DED can include a cycle of inflammation involving both innate and adaptive immune responses. Recently, in vitro/in vivo models have been used to obtain a better understanding of DED‐related inflammatory processes at molecular/cellular levels although they do not truly reproduce the complex and chronic hallmarks of human DED. In clinical DED research, advanced techniques such as impression cytology, conjunctival biopsy, in vivo confocal microscopy and multiplex tear analyses have allowed an improved assessment of inflammation in DED patients. This was supported by the identification of reliable inflammatory markers including matrix metalloproteinase‐9, human leucocyte antigen‐DR or intercellular adhesion molecule‐1 in tears and impression cytology samples. One of the current therapeutic strategies focuses on breaking the inflammatory cycle perpetuating the ocular surface disease, and preclinical/clinical research has led to the development of promising anti‐inflammatory compounds. For instance, cyclosporine, already approved in the United States, has recently been authorized in Europe to treat DED associated with severe keratitis. In addition, other agents such as corticosteroids, doxycycline and essential fatty acids, through their anti‐inflammatory properties, show encouraging results. We now have a clearer understanding of the inflammatory processes involved in DED, and there is hope that the still emerging preclinical/clinical findings will be translated into new and highly effective therapies for patients in the near future.

To measure matrix metalloproteinase 9 (MMP-9) in the tear film of patients with dry eye disease (DED) compared with controls and to correlate clinical findings.In a prospective study, 101 patients and controls underwent MMP-9 testing of the tear film. Thereafter, they were evaluated for symptoms and signs of DED.Included patients were those who showed 3 of the following 4 dry eye criteria: ocular surface disease index (OSDI) score of more than 12, tear film break-up time (TBUT) of 10 seconds or less, Schirmer test results without anesthesia of less than 10 mm/5 minutes, and corneal staining results of 1 or more. Fifty-four healthy eyes and 47 eyes fulfilling diagnostic criteria for DED of various levels of severity were included in this study.The tear film was analyzed for MMP-9 by a commercially available test (InflammaDry; Rapid Pathogen Screening, Inc, Sarasota, FL) detecting MMP-9 levels of more than 40 ng/ml. Symptoms and signs of DED were evaluated using the OSDI questionnaire, TBUT, conjunctival and corneal staining, Schirmer test results without anesthesia, and meibomian gland examination. These findings were correlated to results of the MMP-9 test in tears.Positive MMP-9 results in tears.In 19 of 47 patients confirmed with dry eye (40.4%) and in 3 of 54 controls (5.6%), the MMP-9 results were positive. This difference was statistically significant (P0.001). Thus, the MMP-9 results indicated a clinically significant inflammation in 40% of dry eye patients. Positive results correlated well with subjective symptoms of DED evaluated by OSDI (P = 0.001), TBUT of less than 5 seconds (P0.013), Schirmer test results (P0.001), conjunctival staining (P0.001), and corneal staining (P = 0.007). Moreover, MMP-9 results correlated with the number of obstructed meibomian ducts (P = 0.005) and a pathologic meibomian gland secretion (P = 0.001). The MMP-9 results were increased significantly in women (P0.001) and in patients with autoimmune disease (P = 0.005), especially Sjögren's syndrome (P = 0.001) and thyroid disease (P = 0.012).Matrix metalloproteinase 9 testing in DED is a valuable new diagnostic tool. It correlated well with other dry eye tests and identified the presence of ocular surface inflammation in 40% of confirmed dry eye patients. It may be especially helpful to identify patients with ocular surface inflammation and autoimmune disease and may facilitate the decision to institute anti-inflammatory treatment in these patients.

Meibomian gland dysfunction (MGD) is a common and chronic disorder that has a significant adverse impact on patients' quality of life. It is a leading cause of evaporative dry eye disease (DED), as meibomian glands play an important role in providing lipids to the tear film, which helps to retard the evaporation of tears from the ocular surface. MGD is also often present in conjunction with primary aqueous-deficient DED. Obstructive MGD, the most commonly observed type of MGD, is the main focus of this article. MGD is probably caused by a combination of separate conditions: primary obstructive hyperkeratinization of the meibomian gland, abnormal meibomian gland secretion, eyelid inflammation, corneal inflammation and damage, microbiological changes, and DED. Furthermore, skin diseases such as rosacea may play a part in its pathology. Accurate diagnosis is challenging, as it is difficult to differentiate between ocular surface diseases, but is crucial when choosing treatment options. Ocular imaging has advanced in recent years, providing ophthalmologists with a better understanding of ocular diseases. This review presents a literature update on the 2011 MGD workshop and an optimized approach to accurate diagnosis of MGD using currently available methods and tests. It also outlines the emerging technologies of interferometry, non-contact meibography, keratography and in vivo confocal laser microscopy, which offer exciting possibilities for the future. Selected treatment options for MGD are also discussed.

The purpose of this study was to determine the quantity and distribution of antigen presenting cells (APC) in various inflammatory and non-inflammatory corneal diseases, comparing in vivo confocal microscopy (IVCM) and immunohistochemistry.Corneae of 41 eyes, composed of group 1 (status post herpes-keratitis), group 2 (keratoconus) and group 3 (graft rejection after keratoplasty) were investigated. IVCM was used preoperatively to assess the distribution and density of dendritic cells in the corneal center versus the paracentral area. Afterwards, all patients underwent penetrating keratoplasty. The host corneas were analyzed by immunohistochemistry for antigen presenting cell distribution, density and characterization by using specific markers for CD207/Langerin, CD209/DC-SIGN and HLA-DR. The IVCM findings were compared with immunohistochemistry results in the corneal epithelium.Cells with branching dendritic morphology were visualized by IVCM mainly in the basal epithelial layer and subepithelial nerve plexus of the central and paracentral cornea. The density of APC in IVCM decreased in all groups towards the central part of the cornea. The highest gradient was observed in group 2, followed by groups 1 and 3. The corneal paracenter showed similiar distribution of APC in group 1 and 2 (76.7 cells/mm(2) and 74.4 cells/mm(2)). The highest density of central APC was observed in group 1 (53.76 cells/mm(2)), followed by group 3 (27.0 cells/mm(2)) and group 2 (24.2 cells/mm(2)). In immunohistochemistry positive stained, APC were distributed similarly to IVCM but with a higher density (p0.05).Distribution, density and stage of maturation of corneal epithelial APCs can be evaluated on morphological basis by IVCM. However, the corneal APCs density was about three-fold lower compared to immunohistochemistry findings.

Ocular chronic graft-versus-host disease (cGVHD) is one of the most frequent long-term complications after hematopoietic stem cell transplantation and is often associated with significant morbidity and reduced quality of life.The German/Austrian/Swiss Consensus Conference on Clinical Practice in cGVHD aimed to summarize the currently available evidence for diagnosis and (topical) treatment and to summarize different treatment modalities of ocular cGVHD. The presented consensus was based on a review of published evidence and a survey on the current clinical practice including transplant centers from Germany, Austria, and Switzerland.Ocular cGVHD often affects the lacrimal glands, the conjunctiva, the lids (including meibomian glands), and the cornea but can also involve other parts of the eye such as the sclera. Up to now, there have been no pathognomonic diagnostic features identified. The main therapeutic aim in the management of ocular cGVHD is the treatment of inflammation and dryness to relieve patients' symptoms and to maintain ocular integrity and function. Therapy should be chosen in the context of the patient's overall condition, systemic immunosuppressive therapy, symptoms, ocular surface integrity, and inflammatory activity. The consensus conference proposed new grading criteria and diagnostic recommendations for general monitoring of patients with graft-versus-host-disease for use in clinical practice.The evidence levels for diagnosis and treatment of ocular cGVHD are low, and most of the treatment options are based on empirical knowledge. Topical immunosuppression, for example, with cyclosporine, represents a promising strategy to reduce inflammation and dryness in ocular cGVHD. Further clinical trials are necessary to elucidate risk factors for eye manifestation, complications, and visual loss and to evaluate staging criteria and diagnostic and therapeutic measures for ocular cGVHD.

This report describes a 12-year-old girl with diffuse infiltrating retinoblastoma. This inflammatory condition belongs to the uveitis masquerade syndromes, which comprise a group of various ocular diseases such as chronic intraocular inflammation and ocular tumors.

Advanced diabetic keratopathy includes impaired corneal sensation, reduced tear secretion, conjunctival squamous metaplasia, and goblet cell loss, as well as susceptibility to corneal erosions and ulcerations. It is thought to be a form of generalized diabetic neuropathy. Early diagnosis of nerve fiber degeneration is essential to prevent further damage. We examined the corneal innervation pattern of patients with diabetes mellitus type 1 and 2 of various durations by in vivo confocal microscopy, and correlated our findings to the severity of diabetic retinopathy, corneal sensation, peripheral diabetic neuropathy in the lower limb, and nephropathy. Nerve fiber length (NFL) was significantly different between patients without diabetic retinopathy and controls (p = 0.028). In patients with non-proliferative diabetic retinopathy (NPDR) and patients with proliferative diabetic retinopathy (PDR), nerve fiber parameters including density (NFD), NFL, and corneal nerve branching (NB) showed a difference with increasing significance compared to healthy persons. A history of nephropathy and/or peripheral neuropathy (all p

Vernal keratoconjunctivitis (VKC) is a chronic, seasonally exacerbated allergic inflammation of the lids, conjunctiva, and cornea. The pathogenesis of VKC is much more complex than a mere type I hypersensitivity reaction. T-cell-mediated responses, eosinophil attraction, and nonspecific immunological reactions are key mechanisms involved. Cytokines, chemokines, proteases, and growth factors play a major pathogenetic role. Therapeutic options in VKC include mast cell stabilizers, antihistamines, corticosteroids, and immunosuppressive drugs. Newer, more selective therapeutic strategies such as antichemokine receptor antibodies, leukotriene receptor antagonists, and specific macrobiomolecules are under evaluation.

In vivo confocal microscopy (IVCM) is able to demonstrate the characteristic corneal and conjunctival anatomy in vivo at the cellular level. Normal corneal innervation and cell distribution, as well as changes associated with age, contact lens wear and systemic disease such as diabetes, can be documented in vivo with this technique. IVCM is helpful to differentiate corneal dystrophies and inclusion keratopathies. Infectious agents, such as fungi and Acanthameba, may be visualized directly in the cornea in keratitis. Postsurgical applications include its use following refractive surgery, UV-crosslinking, keratoplasty and amniotic membrane transplantation to evaluate corneal wound healing. Conjunctivalization of the cornea in presumed limbal insufficiency can also be shown by IVCM. Laser scanning IVCM also allows the examination of conjunctival structures, as well as the lid margin. Thus, IVCM may help to establish a final diagnosis in atypical conjunctival inflammation and uncharacteristic conjunctival tum...

Corneal cross-linking is widely used to treat keratoconus. However, to date, only limited data from randomized trials support its efficacy. The efficacy and safety of corneal cross-linking for halting progression of keratoconus were investigated in a prospective, randomized, blinded, placebo controlled, multicentre trial. Twenty-nine keratoconus patients were randomized in three trial centres. The mean age at inclusion was 28 years. Longitudinal changes in corneal refraction were assessed by linear regression. The best corrected visual acuity, surface defects and corneal inflammation were also assessed. These data were analysed with a multifactorial linear regression model. A total of 15 eyes were randomized to the treatment and 14 to the control group. Follow-up averaged 1098 days. Corneal refractive power decreased on average (+/−standard deviation) by 0.35 +/− 0.58 dioptres/year in the treatment group. The controls showed an increase of 0.11 +/− 0.61 dioptres/year. This difference was statistically significant (p = 0.02). Our data suggest that corneal cross-linking is an effective treatment for some patients to halt the progression of keratoconus. However, some of the treated patients still progressed, whereas some untreated controls improved. Therefore, further investigations are necessary to decide which patients require treatment and which do not. NCT00626717 , Date of registration: February 20, 2008.

The 77th meeting of the Association for Research in Vision and Ophthalmology (ARVO) presented the latest developments in clinical research and practice across a range of ophthalmic disciplines. Of particular interest was the current status of research in dry eye and ocular allergy. With these conditions being very common to ophthalmologists, and the fact that they are difficult to differentiate due to the number of overlapping symptoms, there remains a need for more rapid and accurate methods for their diagnosis. Therefore, a number of new tools were presented that have the potential for use in clinical trials and practice to improve the diagnosis and assessment of dry eye and ocular allergy. Some of these tools have been developed based on a greater understanding of the pathophysiology of dry eye and ocular allergy, and the various molecular pathways involved. Indeed, a greater understanding of the molecular mechanisms involved in the pathogenesis of dry eye and ocular allergy has identified potential targets for the treatment of these conditions. Continuing research into new agents can provide ophthalmologists with a number of options that will ultimately benefit the patient.

To analyze the appearance of conjunctival pigmented tumors as seen by in vivo confocal microscopy. Twenty-eight pigmented conjunctival tumors including 6 nevi, 13 acquired melanoses, 7 conjunctival melanomas, and 2 extrascleral growths of uveal melanomas were examined by in vivo confocal microscopy using the Heidelberg Retina Tomograph (HRTII)/Rostock Cornea Modul (RCM). Confocal images were analyzed using predefined criteria by an observer masked to final histological diagnosis and a preliminary diagnosis was established. After excision, histology and immunohistochemistry using antibodies against S-100, Melan-A, HMB-45, Ki-67, CD3, and CD68 were performed in all specimens and compared with in vivo confocal images of the same lesions. Confocal microscopy images confirmed typical histopathological features of conjunctival pigmented tumors. Nest or diffuse collections of medium-sized uniform hyper- or hyperreflective cells in the stroma and stromal cysts lined with a multilayered epithelium were visible in 100% of conjunctival nevi. Small dendritic cells were typically observed in 100% of primary acquired melanoses (PAM) without atypia and in 2 out of 6 nevi. Large networks of hyperreflective dendritic cells were present in 100% of PAM with atypia. Whereas images of PAM without atypia and secondary complexion-associated melanosis showed hyperreflective granules confined to the basal epithelium in 67% of lesions, PAM with atypia presented with hyperreflective granules and patches throughout the epithelium in all cases. Malignant melanomas of the conjunctiva and extrascleral growths of uveal melanomas demonstrated large hyperreflective cells with prominent nuclei and nucleoli. In vivo confocal microscopy showed a sensitivity of 89% and a specificity of 100% to establish the correct diagnosis of conjunctival melanoma compared with histology. High correlations were found between in vivo confocal microscopy using near-infrared laser light and histology in the diagnosis of pigmented conjunctival lesions. In vivo confocal microscopy seems to be a valuable new tool in the differential diagnosis and follow-up of pigmented conjunctival tumors. It does not replace histology, but may assist in performing guided biopsy in tumors suspected clinically and/or with in vivo microscopy. In addition, in vivo confocal microscopy may support the clinical diagnosis of extrascleral involvement in uveal melanoma.

Objective Keratitis–ichthyosis–deafness (KID) syndrome is a rare congenital ectodermal dysplasia characterized by the association of hyperkeratotic skin lesions, moderate to profound sensorineural hearing loss and vascularizing keratitis. Mutations in the GJB2 gene coding for connexin 26, a component of gap junctions in epithelial cells, have been observed in several KID patients. Variable ocular manifestations of the disease in 3 patients with molecular genetically confirmed KID syndrome are reported. Design Retrospective case series. Methods Clinical examination and molecular genetic analysis for mutations in the GJB2 gene were performed in 3 patients with KID syndrome ages 5, 13, and 41 years. Results Visual acuity ranged from normal to severe visual loss. The ocular signs included loss of eyebrows and lashes, thickened and keratinized lids, trichiasis, recurrent corneal epithelial defects, superficial and deep corneal stromal vascularization with scarring, keratoconjunctivitis sicca, and, in one patient, presumed limbal insufficiency. Whereas ocular surface integrity could be maintained with artificial tears in one patient, and an epithelial defect healed under conservative treatment in the second patient, multiple surgical procedures including superficial keratectomies, limbal allograft transplantation with systemic immunosuppression, amniotic membrane transplantation, lateral tarsorrhaphies, and lamellar keratoplasty could not preserve useful vision in the third patient. Conclusions KID syndrome may affect the ocular adnexae and surface with variable severity independent of the age of the patient. Lid abnormalities, corneal surface instability, limbal stem cell deficiency with resulting corneal complications, and dry eye are the main ocular manifestations.

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.

Background Dysfunction of the meibomian glands with inflammation and obstruction has been suggested to be an important factor in the pathogenesis of chronic blepharitis. Few objective tests are, however, available to examine the meibomian glands directly. Patients and methods Nineteen patients with anterior blepharitis, meibomitis, meibomian gland dysfunction or severe keratoconjunctivitis sicca associated with blepharitis as well as 10 patients with normal lid margins were examined with the HRTII/RCM in vivo confocal microscope. Scans of the tear film, the tarsal conjunctiva, the hair follicles and the meibomian glands were analysed by a masked observer. Results Patients with normal lid margins exhibited a minimal round cell infiltrate in the tarsal conjunctival epithelium and largely normal ducts of the meibomian glands lined with a multilayered epithelium as well as normal gland acini. In patients with anterior blepharitis, blepharitis associated with autoimmune peripheral ulcerative keratitis and blepharitis in the context of severe dry eye, confocal microscopy disclosed normal meibomian glands. In 12 patients with blepharitis/meibomitis or meibomian gland dysfunction, profound pathology was visible with dilatation and obstruction of the meibomian gland ducts. In 15 of 19 patients with blepharitis/meibomitis, but not in meibomian gland dysfunction, an intense inflammation was observed in the tarsal conjunctival epithelium and stroma. In one patient, demodex folliculorum was evident in vivo. In patients with normal lid margins as well as in patients with blepharitis, hair follicles appeared within normal limits. Conclusions In vivo confocal microscopy allowed the examination of the tear film, the tarsal conjunctiva, the lid margin including the lash follicles and the meibomian glands. In patients with meibomian gland disease pathological changes could be visualised and documented objectively. The presence of an inflammatory infiltrate permitted us to differentiate between meibomitis and meibomian gland dysfunction. Changes of the lash follicles do not seem to play an important role in blepharitis. Thus, in vivo confocal microscopy represents an objective technique in the classification and follow-up of patients with blepharitis.

A dense cataract prevents detailed fundus examination which may lead to delayed diagnosis of undiscovered intraocular pathology before cataract surgery. We report two cases where large choroidal melanomas were diagnosed after cataract surgery and/or Nd:Yag laser capsulotomy. In the first case, a dense cataract prevented proper examination of the fundus of an 84-year-old female. A brownish choroidal lesion was seen after cataract surgery and diagnosed as postoperative choroidal detachment. As this lesion persisted over months, the patient was sent to our hospital for evaluation where a diagnosis of choroidal melanoma with extrascleral growth was made and an enucleation with implantation of a dermis-fat graft was performed without complication 10 days later. In the second case, a 58-year-old female patient had Nd:Yag laser treatment 2 years after cataract surgery had been performed. During fundus examination 1 day after treatment, the ophthalmologist noticed a choroidal lesion which he suspected to be a reaction to the laser treatment and referred the patient to our hospital where a diagnosis of a mushroom-shaped choroidal melanoma with serous retinal detachment was made. These cases show that preoperative evaluation of the posterior segment prior to cataract surgery or other therapeutic interventions is essential in order to identify any pathology. In case of a dense cataract, additional imaging such as ultrasound sonography is recommended in order to exclude intraocular lesions and to visualize the optic disc in suspected glaucoma.

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

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.

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 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.

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

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.

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.