Patient-reported burden and overall impact of dry eye disease across eight European countries: a cross-sectional web-based survey.

OBJECTIVE: Dry eye disease (DED) is a multifactorial disease involving the tears and ocular surface. It impacts a patient's quality of life (QoL) and ability to perform daily activities. This study assessed the burden of self-reported DED among adults in eight European countries. DESIGN: Online cross-sectional survey. SETTING: General population in France, Italy, Germany, Greece, the Netherlands, Portugal, Spain and Sweden. PARTICIPANTS: Adults aged ≥18 years with (n=6084) and without (n=6161) self-reported DED were recruited via emails and screened. MAIN OUTCOME MEASURES: All participants completed National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQol-5 Dimension-5 Level Questionnaire (EQ-5D-5L). All DED participants completed the Eye Dryness Score (EDS) Visual Analogue Scale, and Ocular Comfort Index and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem questionnaires. In addition, half of the respondents with DED completed Survey A (Impact of Dry Eye on Everyday Life) and the other half completed Survey B (Standard Patient Evaluation of Eye Dryness Questionnaire) and Dry Eye Questionnaire-5. RESULTS: Participants with self-reported DED had lower functional vision and lower overall health status than participants without self-reported DED as measured by the NEI-VFQ and EQ-5D-5L, respectively.Increasing self-reported DED severity as measured by the EDS was shown to correspond with worse symptom severity/frequency, lower functional vision, higher impact on work productivity, daily activities and QoL. CONCLUSION: This study showed that patients' reported burden of self-reported DED was similar across the eight European countries. Those with self-reported DED reported lower health status and functional vision compared to those without self-reported DED and these parameters worsen with increasing disease severity.

Hypopyon after Primary Cryopreserved Amniotic Membrane Transplantation for Sterile Corneal Ulceration: A Case Report and Review of the Literature.

Purpose. To report the acute development of hypopyon after primary cryopreserved amniotic membrane transplantation (AMT) for persistent corneal epithelial defect and sterile ulceration. Case Presentation. A selected case report of a 71-year-old male who underwent primary cryopreserved AMT for the management of long-standing corneal epithelial defects and stroma thinning. The patient developed 2 mm sterile hypopyon within 48 hours after AMT for corneal surface reconstruction. He responded well to the intensified routine postoperative topical treatment of steroid and antibiotic eye drops with the hypopyon resolving completely one week later. Five weeks after surgery, the corneal surface was smooth and epithelialized with no anterior chamber reaction or recurrence of hypopyon. Discussion. Hypopyon may develop as a rare complication of primary cryopreserved AMT for sterile corneal defects. It may be attributed to immunologic or hypersensitivity reaction and should be differentiated from active ocular infection as it resolves spontaneously with the routine postoperative topical treatment of steroid and antibiotic drops.

Revisiting Ocular Allergy: Evaluating Symptoms, Benzalkonium Chloride and Efficacy of Topical Ketotifen 0.025.

This interesting study raises a scientific issue for revisiting three important elements on diagnosis, use of preservatives and selection of the appropriate topical treatment. Itchy feeling can be encountered in other ophthalmic conditions misdiagnosed as allergy, benzalkonium chloride is responsible for surface toxicity resulting in reduced efficacy and tolerability of topical allergy medications and it should be avoided on the management of ocular allergy. Unpreserved ketotifen 0,025% has been shown to be the least toxic formulation being the optimum option for efficacy and tolerability on the management of ocular allergy.

Role of corneal nerves in ocular surface homeostasis and disease.

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.

Controlled Adverse Environment Chambers in Dry Eye Research.

Dry eye disease (DED) is a common condition with signs and symptoms that vary depending on a wide range of environmental factors to which people are exposed in their daily lives. Factors such as variable temperature, airflow velocity, relative humidity, seasonality, and pollutants can alter the rate of tear film evaporation, improving or exacerbating symptoms of DED. Results from currently available clinical tests do not always correlate well with patient-reported symptoms, and the continually changing environment and variability in DED symptoms present challenges for the design and conduct of clinical trials. Controlled adverse environment chambers allow standardization of temperature, humidity, and airflow and may minimize potential confounding factors in clinical investigations. Their use can promote accurate study of the pathophysiology of DED, discovery of disease biomarkers, and assessment of the effect of various therapeutic approaches on patients' symptoms. Controlled adverse environment chambers have been used to simulate indoor surroundings such as airplane cabins and to test their effects on contact lens wearers. This review summarizes how these chambers may be useful for the development, approval, and differentiation of potential new treatments for DED.

Preservative-Free Prostaglandin Analogs and Prostaglandin/Timolol Fixed Combinations in the Treatment of Glaucoma: Efficacy, Safety and Potential Advantages.

Glaucoma therapy-related ocular surface disease (OSD) is a serious pathology with a broad spectrum of insidious clinical presentations and complex pathogenesis that undermines long-term glaucoma care. Preservatives, especially benzalkonium chloride (BAK), contained in topical intraocular pressure-lowering medications frequently cause or aggravate OSD in glaucoma. Management of these patients is challenging, and to date often empirical due to the scarcity of controlled long-term clinical trials. Most of the available data are extracted from case series and retrospective analysis. Preservative-free prostaglandins and prostaglandin/timolol fixed combinations are novel options developed to remove the harmful impact of preservatives, especially BAK, upon ocular tissues. Based on what is currently known on the value of preservative-free antiglaucoma therapies it is tempting to speculate how these new therapies may affect the future medical management of all glaucoma patients. This article provides a comprehensive and critical review of the current literature on preservative-free prostaglandins and preservative-free prostaglandin/timolol fixed combinations.

Emerging strategies for the diagnosis and treatment of meibomian gland dysfunction: Proceedings of the OCEAN group meeting.

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.

Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of meibomian gland dysfunction.

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.

Role of hyperosmolarity in the pathogenesis and management of dry eye disease: proceedings of the OCEAN group meeting.

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 Transplant Infection due to Alternaria alternata: A Case Report.

Purpose. To report a case of Alternaria alternata keratitis in a patient with a corneal transplant in her right eye due to bullous pseudophakic keratopathy. Methods. A 66-year-old female underwent a full-thickness keratoplasty in her right eye due to bullous pseudophakic keratopathy. Three weeks after keratoplasty, epithelial edema and a stromal opacity with an infiltrate and development of peripheral corneal opacities appeared. The diagnosis of Alternaria alternata keratitis was made. Results. The patient underwent a second keratoplasty, due to the corneal melting as a result of the fungal infection. She was also given combined antifungal treatment locally and systematically. Conclusion. Corneal transplantation alone would not have been sufficient to keep the fungus in the anterior portion of the eye. Combined antifungal treatment, locally and systematically, was important in attempting to prevent the further spread of the fungus to the interior of the eye. To our knowledge, the case presented here is only the second one in the literature concerning a keratomycosis due to Alternaria alternata corneal transplant infection.

B-cell targeted therapy with rituximab for thyroid eye disease: closer to the clinic.

The management of thyroid eye disease (TED) remains a therapeutic challenge. The current established therapies are unsatisfactory in one-third of the patients and have many limitations. Rituximab (RTX) is a CD20+ B-cell-depleting monoclonal antibody approved for the treatment of non-Hodgkin lymphomas, chronic lymphocytic leukemia, and rheumatoid arthritis. The early experience with RTX suggests that it is a promising alternative therapy for TED. Rituximab may compare favorably to the conventional glucocorticoid therapy and causes less collateral damage than retrobulbar orbital radiation and decompression surgery. In addition, the preliminary studies on RTX's proposed mechanism of action have revealed new insights into the pathogenic role of B-cells in TED. We summarize the current literature on the clinical application of RTX in TED and discuss its putative mechanisms of action.

Interventions for involutional lower lid entropion.

BACKGROUND: Entropion is a condition in which the eyelid margin turns in against the eyeball. Involutional or senile entropion is one of the most common lower lid malpositions in the elderly. The interventions described and currently used for the treatment of this condition are surgical in nature, although non-surgical temporary medical treatment for the early stages of entropion has also been reported. The relative effectiveness of these interventions has not yet been resolved. OBJECTIVES: To examine the effect of interventions for involutional entropion and to assess whether any method is superior to any other. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to November 2011), EMBASE (January 1980 to November 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),ClinicalTrials.gov (http://clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 2 November 2011. We also searched oculoplastic textbooks, conference proceedings from the European and American Society of Ophthalmic Plastic and Reconstructive Surgery (ESOPRS, ASOPRS), European Ophthalmological Society (SOE), the Association for Recearch in Vision and Ophthalmology (ARVO) and American Academy of Ophthalmology (AAO) for the years 2000 to 2009 to identify relevant data. We attempted to contact researchers who are active in this field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with no restriction on date or language comparing two or more surgical methods for correction of involutional lower eyelid entropion in people older than 60 years of age with involutional lower lid entropion. DATA COLLECTION AND ANALYSIS: Each review author independently assessed study abstracts identified from the electronic and manual searches. Author analysis was then compared and full papers for appropriate studies were obtained according to the inclusion criteria. Disagreements between the authors were resolved by discussion. MAIN RESULTS: We identified one RCT which met our inclusion criteria and was included in this review. Sixty-three participants with primary involutional lower eyelid entropion were randomised to everting sutures alone or everting sutures with a lateral tarsal strip. Eight participants were lost to follow-up. The trial indicates that the combined procedure for horizontal and vertical eyelid tightening in the form of everting sutures and lateral tarsal strip is highly curative for involutional entropion compared to vertical tightening in the form of everting sutures alone. The superiority of the combined approach is also supported by many good quality uncontrolled studies on specific surgical procedures but these were not included in the analysis as they were not part of the inclusion criteria. AUTHORS' CONCLUSIONS: A single RCT showed that the combination of horizontal and vertical eyelid tightening with everting sutures and lateral tarsal strip is highly efficient for entropion compared to vertical tightening with everting sutures alone. Retrospective case series studies also support the combined surgical repair but details from these studies on specific surgical techniques cannot be included in the analysis.Evidence from a single RCT is unlikely to change clinical practice and thus it is still our view that there is a clear need for more randomised studies comparing two or more surgical techniques for entropion surgery addressing the recurrence and complications rate.

Surgical orbital decompression for thyroid eye disease.

BACKGROUND: Orbital decompression is an established procedure for the management of exophthalmos and visual rehabilitation from optic neuropathy in cases of thyroid eye disease. Numerous procedures for removal of orbital bony wall, fat or a combination of these for a variety of indications in different stages of the disease have been well reported in the medical literature. However, the relative effectiveness and safety of these procedures in relation to the various indications remains unclear. OBJECTIVES: To review current published evidence for the effectiveness of surgical orbital decompression for disfiguring proptosis in adult thyroid eye disease and summa rise information on possible complications and the quality of life from the studies identified. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to October 2011), EMBASE (January 1980 to October 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (http://clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 October 2011. We searched oculoplastic textbooks, conference proceedings from the European and American Society of Ophthalmic Plastic and Reconstructive Surgery (ESOPRS, ASOPRS), European Ophthalmological Society (SOE), the Association for Research in Vision and Ophthalmology (ARVO) and American Academy of Ophthalmology (AAO) for the years 2000 to 2009 to identify relevant data. We attempted to contact researchers who are active in this field for information about further published or unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with no restriction on date or language comparing two or more surgical methods for orbital decompression with removal of bony wall, orbital fat or a combination of both for disfiguring proptosis or comparison of surgical techniques with any form of medical decompression. DATA COLLECTION AND ANALYSIS: Each review author independently assessed study abstracts identified from the electronic and manual searches. Author analysis was then compared and full papers for appropriate studies were obtained according to the inclusion criteria. Disagreements between the authors were resolved by discussion. MAIN RESULTS: We identified two randomised trials eligible for inclusion in the review. There was significant variability between the trials for interventions, methodology and outcome measures and therefore meta-analysis was not performed. One study suggested that the transantral approach and endoscopic transnasal technique had similar effects in reducing exophthalmos but that the endoscopic approach may be safer, relating to fewer complications. This study had short-term follow-up and lacked information on our primary outcome (success or failure of treatment). The second study provided evidence that intravenous steroids may be superior to primary surgical decompression in the management of compressive optic neuropathy requiring less secondary surgical procedures, although it relates more frequently to transient side effects. This study was weakened by a small sample size. Until more credible evidence is available recommendations as to best treatment cannot be reliably made. AUTHORS' CONCLUSIONS: A single study showed that the transantral approach for orbital decompression was related to more complications than the endoscopic transnasal technique which is preferred by Ear, Nose and Throat (ENT) surgeons, usually as an adjunctive procedure. Intravenous steroids were reported in a single trial to be the most efficient intervention for dysthyroid optic neuropathy. The majority of published literature on orbital decompression for thyroid eye disease consists of retrospective, cohort, or case series studies. Although these provide useful descriptive information, clarification is required to show the relative effectiveness of each intervention for various indications.The two RCTs reviewed are not robust enough to provide credible evidence to our understanding of current decompressive surgery and to support recommendations for clinical practice. There is evidence from currently available uncontrolled studies that removal of the medial and lateral wall (balanced decompression) with or without fat removal may be the most effective surgical method related to only a few complications.There is a clear need for randomised studies evaluating the balanced two-wall, three-wall and orbital fat decompression techniques. Comparison with other surgical techniques for orbital decompression or with immunosuppression in cases of compressive optic neuropathy would also be important. These studies should primarily address the reduction of exophthalmos, disease severity, complication rates, quality of life and cost of the intervention.

Kaposi's Sarcoma of the Bulbar Conjunctiva in an Immunocompetent Patient.

Kaposi's sarcoma is an uncommon endothelial malignant tumor, first described by Moricz Kaposi in 1872. It is commonly encountered in patients with acquired immunodeficiency syndrome (AIDS), immunosuppression or organ transplantation. Conjunctival Kaposi's sarcoma is a rare tumor, mostly in patients with AIDS. We present a selected case with a superior bulbar conjunctival lesion in a patient who is HIV negative and immunocompetent, with an unremarkable general medical history. The lesion was surgically excised with no adjunctive treatment, and histological examination confirmed the diagnosis. There was no recurrence or metastasis 5 years after surgery.

Childhood orbitotemporal neurofibromatosis masked by congenital glaucoma and buphthalmos.

In newborns with unilateral buphthalmos and presumed congenital glaucoma, the differential diagnosis should include the rare condition of orbitotemporal neurofibromatosis. The authors present the diagnostic challenge of an unusual case of neurofibromatosis type 1 with unilateral congenital glaucoma, buphthalmos, and sphenoid-orbital dysplasia. The accompanying type of osseous orbital dysplasia has rarely been described in the literature, complicating the diagnostic and management process.

Orbital fat decompression for Graves' orbitopathy: a literature review.

Thyroid eye disease manifests as orbital inflammation resulting in extraocular muscle enlargement and orbital fat proliferation. This causes exophthalmos, ocular motility impairment and eyelid retraction. Numerous surgical procedures have been introduced for correction of exophthalmos by removal of bony walls. The limited success and high complication rate of the early methods lead to the evolution of an alternative procedure for reduction of retrobulbar volume by removal of intraorbital fat. The indications for this procedure extended from orbital decompression to compressive optic neuropathy with satisfactory results. The moderate complication rate and the fact that orbits with predominant muscle enlargement respond purely to this technique leads to the evolution of a combined procedure with orbital fat removal and bony wall decompression. The scattered published evidence comprising retrospective case series highlights the need for prospective controlled clinical trials in order to improve patient care and clinical practice.

Management of canalicular obstructions.

PURPOSE OF REVIEW: The successful treatment of canalicular obstructions continues to represent a therapeutic challenge. Conjuctivodacryocystorhinostomy with a Lester Jones bypass tube is the standard treatment in these situations. Although a high rate of anatomic success can be achieved with this procedure, a relatively high rate of complications and poor patient satisfaction have been reported. Because of this, alternative techniques have emerged. Herein, we review all these techniques described in the literature. RECENT FINDINGS: Increasing interest in minimally invasive surgery and developments in fiberoptic technology have fueled advances in endocanalicular surgery. Canalicular trephination for obstructions at any level of the canalicular system and laser and balloon canaliculoplasty for focal canalicular and common canalicular stenoses may offer a well tolerated, fast and easy alternative, with potentially better patient satisfaction when compared with conjuctivodacryocystorhinostomy. SUMMARY: The alternative techniques to conjuctivodacryocystorhinostomy are less invasive, and respect and utilize any healthy and functional part of the canalicular system. The correct choice of the technique for a given canalicular obstruction, and therefore the long-term success, depends on the site and degree of the obstruction.

A modified technique of retrograde intubation dacryocystorhinostomy for proximal canalicular obstruction.

PURPOSE: To describe a modification of the retrograde intubation dacryocystorhinostomy (DCR) in patients with proximal canalicular obstruction. MATERIALS AND METHODS: Interventional case report of a 43-year-old female with a nine-month history of left epiphora following a road traffic accident involving the proximal lower canaliculus. An external DCR approach was performed. Following the creation of a lower canalicular pseudopunctum, the O'Donoghue silicone stent was introduced through the common ostium, out through the pseudopunctum of the lower canaliculus, and returned through the punctum of the normal upper canaliculus down through the common ostium into the nose. RESULTS: The patient experienced complete resolution of symptoms and on her last follow-up, two years later, her lower canaliculus was patent to syringing. CONCLUSION: This modification of the retrograde intubation DCR is an effective technique which decreases the intraoperative time needed to insert the tubes and minimises further trauma to the newly created punctal area.