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To evaluate the effect of IPL (intense pulsed light) treatment in patients with meibomian gland dysfunction (MGD).Clinical data of 25 patients with MGD who underwent IPL treatment at the department of ophthalmology of Ludwig-Maximilians-University between 2016 and 2018 were analyzed. Demographics, clinical history, examination findings (eyelid vascularization, meibomian gland findings, conjunctival redness, tear film break-up time [TFBUT], corneal staining (Oxford grading scale [OGS]), and subjective patients' findings (including ocular surface disease index [OSDI]) were collected from each visit (D1, D15, D45, D75).All included patients underwent three sessions of IPL treatment in both eyes (D1, D15, D45). There was a significant improvement after IPL treatment (D75) in TFBUT (p 0.001), corneal staining (OGS) (p 0.001), conjunctival redness (p 0.001), lid margin edema (p 0.001) and redness (p 0.001), meibum quality (p 0.001), lid margin telangiectasia (p = 0.005), meibomian gland obstruction (p = 0.001), and OSDI score (p = 0.004). Even after the first IPL session, significant improvements in TFBUT (p 0.001), corneal staining (OGS p 0.001), conjunctival redness (p 0.022), lid margin edema (p 0.001) and redness (p 0.016), meibum quality (p = 0.014), and OSDI score (p 0.013) were noted. There were no relevant negative side effects. Subgroup analysis for age, sex, duration or severity of disease, and associated diagnosis of rosacea showed no significant difference in effectiveness.IPL is an effective and safe treatment for patients with MGD, which can be used as a supportive therapeutic option.ZIEL: Beurteilung der Wirkung der IPL-Therapie (IPL: Intensive pulsed Light) bei Patienten mit Meibomdrüsendysfunktion (MDD).Analysiert wurden die Daten von 25 Patienten mit MDD, die zwischen 2016 und 2018 in der Abteilung für Augenheilkunde der LMU mittels IPL behandelt wurden. Demografische Daten, klinische Anamnese sowie Untersuchungsbefunde (Lidrandvaskularisation, Meibomdrüsenbefunde, Bindehautrötung, Tränenfilmaufrisszeit (TFBUT), Hornhautoberflächenfärbung (Oxford Grading Scale [OGS]) und subjektive Symptome (einschließlich des Ocular Surface Disease Index [OSDI]) wurden bei jedem Besuch erhoben (D1, D15, D45, D75).Alle Patienten erhielten eine IPL-Behandlung in 3 Sitzungen an beiden Augen (D1, D15, D45). Am Ende der IPL-Behandlung (D75) zeigte sich eine signifikante Verbesserung von TFBUT (p 0,001), Hornhautoberflächenfärbung (OGS) (p 0,001), Bindehautrötung (p 0,001), Lidrandödem (p 0,001) und Lidrandrötung (p 0,001), Meibumqualität (p 0,001), Lidrandteleangiektasien (p = 0,005), Meibomdrüsenobstruktion (p = 0,001) und OSDI-Score (p = 0,004). Bereits nach der 1. IPL-Sitzung konnte eine signifikante Verbesserung von TFBUT (p = 0,001), Hornhautoberflächenfärbung (OGS p 0,001), Bindehautrötung (p = 0,022), Lidrandödem (p = 0,001) und -rötung (p = 0,016), Meibumqualität (p = 0,014) und OSDI-Score (p = 0,013) festgestellt werden. Es gab keine relevanten negativen Nebenwirkungen. Eine Subgruppenanalyse hinsichtlich Alter, Geschlecht, Dauer oder Schwere der Erkrankung sowie der assoziierten Diagnose der Rosazea zeigte keinen signifikanten Unterschied in der Wirksamkeit.IPL ist eine wirksame und sichere Behandlung für Patienten mit MGD, die als unterstützende therapeutische Option eingesetzt werden kann.

Mucins are key actors in tear film quality and tear film stability. Alteration of membrane-bound mucin expression on corneal and conjunctival epithelial cells and/or gel-forming mucin secretion by goblet cells (GCs) promotes in ocular surface diseases and dry eye disease (DED). Changes in the mucin layer may lead to enhanced tear evaporation eventually contributing to tear hyperosmolarity which has been associated with ocular surface inflammation. Inflammatory mediators in turn may have a negative impact on GCs differentiation, proliferation, and mucin secretion. This sheds new light on the position of GCs in the vicious circle of DED. As contributor to ocular surface immune homeostasis, GC loss may contribute to impaired ocular surface immune tolerance observed in DED. In spite of this, there are no tools in routine clinical practice for exploring ocular surface mucin deficiency/dysregulation. Therefore, when selecting the most appropriate treatment options, there is a clear unmet need for a better understanding of the importance of mucins and options for their replacement. Here, we comprehensively revisited the current knowledge on ocular surface mucin biology, including functions, synthesis, and secretion as well as the available diagnostic tools and treatment options to improve mucin-associated homeostasis. In particular, we detailed the potential link between mucin dysfunction and inflammation as part of the uncontrolled chronic inflammation which perpetuates the vicious circle in DED.

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.

Corneal nerves are key components of the physiological system that controls ocular surface homeostasis. The cornea is primarily innervated by the ophthalmic branch of the trigeminal nerves (cranial nerve V), which distend bilaterally from the pons. The nasociliary branch (afferent) of the ophthalmic nerve is sensory for cornea, eyelid and conjunctiva. These nerve fibres play a role in sensing temperature, chemical and mechanical stimuli, and pain, whereas, branches of the facial nerve (cranial nerve VII) contain motor nerves that control blinking and autonomic (sympathetic and a paucity of parasympathetic) fibres that stimulate tear production and secretion via feedback loops between the ocular surface, lacrimal glands and brain. Disruption of these nerves with interruption of neural feedback loops between the ocular surface and lacrimal glands can lead to corneal diseases such as dry eye disease (DED) and neurotrophic keratopathy (NK). Inversely, hypersensitivity of the nerve fibres and/or dysregulation of pain-controlling nervous centres may lead to neuropathic pain. Recently, medications that specifically target regeneration of corneal nerves have started to become available - and considering the high prevalence of diseases associated with corneal nerve dysfunction, these agents promise to fulfil a hitherto important unmet need. In this review, we explore the physiology of corneal nerves, the pathology of corneal nerve diseases and how these relate to neuropathic pain, NK and DED. We also discuss what novel treatments may be useful against diseases involving corneal nerves.

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.

Dry eye can be caused by a variety of iatrogenic interventions. The increasing number of patients looking for eye care or cosmetic procedures involving the eyes, together with a better understanding of the pathophysiological mechanisms of dry eye disease (DED), have led to the need for a specific report about iatrogenic dry eye within the TFOS DEWS II. Topical medications can cause DED due to their allergic, toxic and immuno-inflammatory effects on the ocular surface. Preservatives, such as benzalkonium chloride, may further aggravate DED. A variety of systemic drugs can also induce DED secondary to multiple mechanisms. Moreover, the use of contact lens induces or is associated with DED. However, one of the most emblematic situations is DED caused by surgical procedures such as corneal refractive surgery as in laser-assisted in situ keratomileusis (LASIK) and keratoplasty due to mechanisms intrinsic to the procedure (i.e. corneal nerve cutting) or even by the use of postoperative topical drugs. Cataract surgery, lid surgeries, botulinum toxin application and cosmetic procedures are also considered risk factors to iatrogenic DED, which can cause patient dissatisfaction, visual disturbance and poor surgical outcomes. This report also presents future directions to address iatrogenic DED, including the need for more in-depth epidemiological studies about the risk factors, development of less toxic medications and preservatives, as well as new techniques for less invasive eye surgeries. Novel research into detection of early dry eye prior to surgeries, efforts to establish appropriate therapeutics and a greater attempt to regulate and oversee medications, preservatives and procedures should be considered.

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.

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.

Aims To demonstrate non-inferiority of a hydroxypropyl guar/polyethylene glycol/propylene glycol lubricating eye-drop (HPG/PEG/PG) compared with an osmoprotective carboxymethylcellulose/glycerine eye-drop (O/CMC) for ocular surface staining. Methods This was a multicentre, randomised, observer-masked, parallel-group study. Adults with dry eye instilled HPG/PEG/PG/ or O/CMC 4 times daily for 35 days and then as needed through day 90. Total ocular surface staining (TOSS) score changes from baseline and Impact of Dry Eye on Everyday Life (IDEEL) treatment satisfaction module scores were assessed. Non-inferiority, based on TOSS score change from baseline, was concluded if the upper limit of the 2-sided CI was Results Mean±SD patient age was 64.4±13.7 years; 94 patients were randomised to treatment (HPG/PEG/PG, n=46; O/CMC, n=48). Mean±SE TOSS score change from baseline to day 35 was −2.2±0.33 with HPG/PEG/PG and −1.7±0.47 with O/CMC (treatment difference, −0.47±0.47; p=0.38), and the non-inferiority criterion was met. IDEEL treatment satisfaction scores were similar between groups at day 35 and day 90. The most frequently reported adverse event was eye irritation (HPG/PEG/PG, n=2; O/CMC, n=3). Conclusions HPG/PEG/PG and O/CMC reduced ocular surface damage, and HPG/PEG/PG was non-inferior to O/CMC. Both treatments were effective, convenient and well tolerated. Trial registration number NCT01863368, Results.

Dry eye disease (DED), a multifactorial disease of the tears and ocular surface, is common and has a significant impact on quality of life. Reduced aqueous tear flow and/or increased evaporation of the aqueous tear phase leads to tear hyperosmolarity, a key step in the vicious circle of DED pathology. Tear hyperosmolarity gives rise to morphological changes such as apoptosis of cells of the conjunctiva and cornea, and triggers inflammatory cascades that contribute to further cell death, including loss of mucin-producing goblet cells. This exacerbates tear film instability and drives the cycle of events that perpetuate the condition. Traditional approaches to counteracting tear hyperosmolarity in DED include use of hypotonic tear substitutes, which have relatively short persistence in the eye. More recent attempts to counteract tear hyperosmolarity in DED have included osmoprotectants, small organic molecules that are used in many cell types throughout the natural world to restore cell volume and stabilize protein function, allowing adaptation to hyperosmolarity. There is now an expanding pool of clinical data on the efficacy of DED therapies that include osmoprotectants such as erythritol, taurine, trehalose and L-carnitine. Osmoprotectants in DED may directly protect cells against hyperosmolarity and thereby promote exit from the vicious circle of DED physiopathology.

Corneal ulceration may be treated with human amniotic membrane (HAM) while neovascularization remains a common complication of corneal ulceration. As several factors contained within HAM may contribute to reduced corneal scarring, we investigated if HAM may be additionally loaded with bevacizumab and potentially serve as a carrier for anti-vascular endothelial growth factor (VEGF) drugs to provide constant VEGF blockade.Cryo-preserved HAM were incubated with different bevacizumab concentrations in organ culture medium for 2-5 d. Controls were incubated without bevacizumab. Then, all samples were placed into an organ culture medium without bevacizumab for 48 h, 72 h or for 5 d at 37 °C with the medium being changed at all time points. After that, VEGF165 was added to the supernatants for 24 h and free VEGF 165 was measured by ELISA.Free VEGF was significantly blocked at 48 and 72 h (p 0.01). VEGF blockade was less pronounced after 1 week. However, as compared to control, VEGF was significantly blocked at all times (p 0.05).In this in-vitro setting, we could demonstrate effective VEGF-blockade for up to 1 week by incubating HAM with bevacizumab. HAMs might be potentially used as a carrier for drugs delivered to the cornea.

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.

Preservatives are a legal requirement for eye drops in multidose containers. Moreover, they are necessary for stabilization and intraocular penetration for a number of ophthalmic preparations. Most preservatives act in a relatively unspecific manner as detergents or by oxidative mechanisms and thereby cause side effects at the ocular surface. They may also affect the lens, trabecular meshwork and the retina. Benzalkonium chloride is the most commonly used preservative in ophthalmology and is more toxic than other or newer preservatives, such as polyquaternium-1 (Polyquad), sodium perborate, oxychloro-complex (Purite®) and SofZia. Preservative-free topical medication is highly recommended for patients with ocular surface disease, frequent eye drop administration, proven allergy to preservatives and contact lens wear.

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.

International audience; Meibomian gland dysfunction (MGD) is the most frequent cause of dry eye disease (DED). Eyelid inflammation, microbial growth, associated skin disorders as well as potentially severe corneal complications culminate to make MGD a complex multifactorial disorder. It is probable that MGD is a heterogeneous condition arising from any combination of the following five separate pathophysiological mechanisms: eyelid inflammation, conjunctival inflammation, corneal damage, microbiological changes and DED resulting from tear film instability. The pathogenesis of both MGD and DED can be described in terms of a 'vicious circle': the underlying pathophysiological mechanisms of DED and MGD interact, resulting in a double vicious circle. The MGD vicious circle is self-stimulated by microbiological changes, which results in increased melting temperature of meibum and subsequent meibomian gland blockage, reinforcing the vicious circle of MGD. Meibomian gland blockage, dropout and inflammation directly link the two vicious circles. MGD-associated tear film instability provides an entry point into the vicious circle of DED and leads to hyperosmolarity and inflammation, which are both a cause and consequence of DED. Here we propose a new pathophysiological scheme for MGD in order to better identify the pathological mechanisms involved and to allow more efficient targeting of therapeutics. Through better understanding of this scheme, MGD may gain true disease status rather than being viewed as a mere dysfunction.

Armin Wolf,1,* Burkhardvon Jagow,2,* Daniel Kook,1 Elisabeth M Messmer,1 Carlo A Lackerbauer,1 Anselm Kampik,1 Thomas Kohnen,2 Martin Grueterich1 1Department of Ophthalmology, Ludwig-Maximilians-Universität, München, 2Department of Ophthalmology, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany *These authors have contributed equallyBackground: With increasing numbers of lamellar keratoplasties, eye banks are challenged to deliver precut lamellar donor tissue. In Europe, the most common technique of corneal storage is organ culture which requires a deswelling process before surgical processing. The aim of this study was to investigate the influence of different deswelling times on the cutting plane quality after microkeratome-assisted lamellar dissection.Methods: Eight paired donor corneas (16 specimens) not suitable for transplantation were organ cultured under standard conditions at the Eye Bank of the Ludwig-Maximilians Universität, Munich, Germany. Pairs of corneal buttons were analyzed during the deswelling process in dextrane-containing medium. While one cornea was cut at an early time point during the deswelling process and put back into deswelling medium thereafter, the partner cornea was completely deswollen and dissected after 72 hours. Specimens were then further processed for scanning electron microscopy. Surface quality was assessed both digitally using Scanning Probe Imaging Processing software, and manually by three blinded graders.Results: The corneal buttons processed at the beginning of the deswelling process had a smoother surface when compared to the partner cornea that was cut at the end of the deswelling process. In our setting, no relevant difference was detectable between manual and automated microkeratome dissection.Conclusion: For lamellar keratoplasty, organ-cultured corneas should be processed at an early stage during the deswelling process. We interpret the smoother dissection plane during early deswelling as a result of mechanical properties in a highly hydrated cornea.Keywords: keratoplasty, deswelling, corneas, microkeratome

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.

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...

Purpose The objective of this study was to compare the efficacy and safety of a polyethylene glycol/propylene glycol based eye drop (PEG/PG; Systane® Ultra) to an osmoprotective-carboxymethylcellulose based eye drop (CMC/O; Optive®) in patients with dry eye. Methods This was a multicenter, observer masked, parallel-design study, subjects were randomized to PEG/PG or CMC/O QID for 35 days (Phase 1) and then as needed for 55 days (Phase 2). Eligible subjects were diagnosed with dry eye and exhibited signs and symptoms at screening. Supportive efficacy assessments included the total ocular staining score (TOSS) score change from baseline to Day 90 (15-point Oxford scale). Results Demographic characteristics were similar between the PEG/PG (n = 46) and CMC/O groups (n = 48). The efficacy of PEG/PG was similar to CMC/O at Day 90 (LS mean treatment difference in TOSS score change from baseline to Day 90 of −0.10 units in favor of PEG/PG). In addition, ocular surface staining associated with dry eye decreased following treatment with PEG/PG with a mean TOSS score change from baseline at Day 90 of −2.7 units. No treatment-related serious adverse events were reported. Five subjects discontinued due to treatment-related AEs (2 PEG/PG and 3 CMC/O subjects). Conclusions PEG/PG based drop demonstrated comparable efficacy to the CMC/O based drop after 90 days treatment with a favorable safety profile in patients with dry eye.

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.

Dry eye disease (DED) is common; its prevalence around the world varies from 5% to 34%. Its putative pathogenetic mechanisms include hyperosmolarity of the tear film and inflammation of the ocular surface and lacrimal gland. Dry eye is clinically subdivided into two subtypes: one with decreased tear secretion (aqueous-deficient DED), and one with increased tear evaporation (hyperevaporative DED).This review is based on pertinent publications retrieved by a selective PubMed search and on the authors' own clinical and scientific experience.The diagnostic evaluation of dry eye disease should include a detailed patient history, thorough split-lamp examination, and additional tests as indicated. Few randomized controlled therapeutic trials for dry eye have been published to date. Artificial tears of various kinds are recommended if the symptoms are mild. Lid hygiene is helpful in the treatment of hyperevaporative dry eye, while collagen or silicon plugs can be used for partial occlusion of the efferent lacrimal ducts to treat severe hyposecretory dry eye. The benefit of long-term topical anti-inflammatory treatment of moderate or severe dry eye disease with corticosteroids or cyclosporine A eye drops has been documented in clinical trials on a high evidence level. Orally administered tetraycycline derivatives and omega-3 or omega-6 fatty acids are also used.The treatment of dry eye has evolved from tear substitution alone to a rationally based therapeutic algorithm. Current research focuses on pathophysiology, new diagnostic techniques, and novel therapies including secretagogues, topical androgens, and new anti- inflammatory drugs.

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.

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.

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.

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

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

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.

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.

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

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.

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.

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.

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.

Multiple papers have reported differences in outcome of choroidal neovascularization (CNV) due to age-related macular degeneration (ARMD) compared to other causes, but few have compared intra-and postoperative outcome of different CNV types in ARMD. Several papers have also described histopathological features of these membranes and their correlation with angiography, but scant information exists of intraoperative findings in correlation to both histopathology and angiography. Furthermore, it has been mentioned that surgically extracted membranes are larger than expected from the preoperative angiography. Unpublished data from Berger and colleagues reported a postoperative RPE-defect that was 145% larger than the original CNV. However, no information was given about the extracted CNV type or a possible intraoperative trauma.