HMG-CoA reductase expression in human eyelid tissue and in a human meibomian gland epithelial cell line.

PURPOSE: 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of cholesterol production, has been found to contribute to lipid secretion from skin sebaceous glands and hair follicles. We assessed for HMGCR expression in human eyelid tissue and in immortalized human meibomian gland epithelial cells (HMGECs) using immunohistochemistry. METHODS: Full thickness human eyelid specimens in archival paraffin blocks were obtained. A section from each block was stained with hematoxylin and eosin and examined by an ocular pathologist for validation of tissue pathology. Immunohistochemistry was performed using rabbit anti-human HMGCR antibody on serial sections using the Ventana automated staining system. HMGCR expression was examined for in HMEGCs with fluorescence immunocytochemistry and confocal microscopy. RESULTS: Thirteen full thickness eyelid specimens met the inclusion criteria. All specimens contained meibomian glands, and 2 (15%) contained glands of Zeis, 3 (23%) pilosebaceous glands, 2 (15%), accessory lacrimal glands, and 2 (15%), glands of Moll, respectively. Immunohistochemistry showed HMGCR expression in meibocytes of meibomian glands and sebocytes of Zeis and pilosebaceous glands in all specimens. HMGCR expression was also evident in vascular endothelium. Immunofluorescence was positive for HMGCR expression on HMGEC cells. No labeling was seen for the negative Ig control. CONCLUSION: HMGCR was expressed in all eyelid sebaceous-type glands and in HMGECs, consistent with a role for cholesterol production in the genesis of tear film lipids. The observed expression also provides a rationale for using topical statins, inhibitors of HMGCR, as novel tear film lipid stabilizers in conditions such as blepharitis, where meibum production is aberrant.

Effectiveness of pharmaceutical interventions for meibomian gland dysfunction: An evidence-based review of clinical trials.

Meibomian gland dysfunction is one of the most common ocular disorders encountered by ophthalmologists and is the leading cause of evaporative dry eye. The disease causes significant morbidity in the population such that patients seek treatment. Multiple clinical studies on pharmacological and mechanical interventions for the treatment of meibomian gland dysfunction have been evaluated. However, there is limited comparative clinical evidence for the effectiveness of these interventions. This review paper aims to report the clinical evidence for pharmaceutical interventions for meibomian gland dysfunction in order to guide clinicians in the management of the disease.

Association of dyslipidaemia and oral statin use, and dry eye disease symptoms in the Blue Mountains Eye Study.

IMPORTANCE: There is limited literature on oral statin use and its association with dry eye. BACKGROUND: To analyse the association between dyslipidaemia, use of oral statin drugs, and symptoms of dry eye disease (DED) among older adults. DESIGN: Population-based study. PARTICIPANTS: Participants of the Blue Mountains Eye Study III (BMESIII), a large cohort study in suburban Sydney, aged 60 years or older (mean age = 74, range = 60-97, n = 1680) were analysed. METHODS: Information on DED symptoms and statin use were obtained from an interviewer-administered questionnaire. Serum lipid profiles were determined from fasting blood tests. MAIN OUTCOME MEASURES: The association of various DED symptoms, as well as their number and their severity, with dyslipidaemia and oral statin intake was evaluated. RESULTS: At least one DED symptom was reported in 52% (n = 1029) of the population. Patients with hypercholesterolaemia (>5.5 mmol/L) did not report more DED symptoms than those without hypercholesterolaemia. Neither serum high-density lipoprotein nor low-density lipoprotein levels were associated with any DED symptoms. Patients taking oral statins were more likely to report one or more moderate to severe symptoms of DED (odds ratio: 2.054, 95% confidence interval: 1.281-3.295). CONCLUSIONS AND RELEVANCE: The association between oral statin use and presence of moderate to severe DED symptomatology is a novel finding that deserves further mechanistic and clinical correlation in order to determine its potential, or lack thereof, for the management of dry eye.

Spontaneous hyphaema secondary to bleeding from an iris vascular tuft in a patient with a supratherapeutic International normalised ratio: case report.

BACKGROUND: Iris vascular tufts are rare iris stromal vascular hamartomas. Patients with iris vascular tufts generally remain asymptomatic until presenting with a spontaneous hyphaema or with mild intraoperative pupil margin haemorrhage during anterior segment surgery. This is the first reported case of spontaneous hyphaema from iris vascular tuft related to a documented supratherapeutic International Normalised Ratio as a predisposing factor. At 86 years of age, this patient also represents the oldest documented first occurrence of bleeding from an iris vascular tuft. CASE PRESENTATION: An 86 year old Caucasian lady presented with sudden and persisting loss of vision in her right eye, ocular pain and vomiting. She had a supratherapeutic International Normalised Ratio of 3.9 related to Warfarin use. Her intraocular pressure in the right eye was raised at 55 mmHg, with a 1.6 mm hyphaema and multiple iris vascular tufts visible around the entire pupil. CONCLUSION: The present case highlights the risk of anticoagulation therapy as a predisposing factor for spontaneous hyphaema and adds to the management considerations for this condition. It also demonstrates the need for Ophthalmologists to be aware of iris vascular tufts as a cause for spontaneous hyphaema, independent of age and systemic associations.

Efficacy and Safety of Topical Atorvastatin for the Treatment of Dry Eye Associated with Blepharitis: A Pilot Study.

AIMS: To elucidate if topically applied atorvastatin safely decreases corneal fluorescein staining in dry eyes associated with blepharitis. METHODS: Ten dry eye and blepharitis (DEB) patients were enroled in a prospective pilot study. All patients were treated with topical atorvastatin (50 µM) 8 times a day for 4 weeks and allowed to continue with their existing dry eye treatment. The patients were examined weekly for 4 weeks. The primary outcome measure was corneal fluorescein staining. Secondary outcome measures were tear film break-up time (BUT), Schirmer I testing, blepharitis score and bulbar conjunctival injection. The subjective efficacy was evaluated with global symptom and facial analogue scores. RESULTS: An improvement in corneal fluorescein staining in the treated eye by >1 point from baseline to completion of the trial at week 4 was found in 9 of 10 patients (p < 0.01). Topical atorvastatin significantly improved the tear film BUT (p < 0.01), blepharitis score (p < 0.05) and bulbar conjunctival injection (p < 0.05). The global symptom score and facial analogue score also improved (p < 0.05). There were no side effects. CONCLUSION: Topical atorvastatin is a potential therapy for DEB patients. Larger comparative clinical studies are required to establish the efficacy and safety of topical atorvastatin.

Motilin Receptor Expression Found in the Human Main and Accessory Lacrimal Glands.

INTRODUCTION: In this study, we investigated the presence of motilin receptors (MR) in adnexal tissue including the human main lacrimal gland. METHOD: 17 adnexal human specimens comprising of 11 isolated human main lacrimal gland specimens, four full-thickness human eyelid excisions and two exenterations containing full-thickness eyelid and portions of the main lacrimal gland were immunolabelled with a rabbit polyclonal human MR antibody. RESULTS: Our results demonstrated that all main lacrimal gland specimens (13/13, 100%) were positive for MR expression with a predominance (10/13 (77%) of grade 1+ punctate distribution. Motilin receptors were not found in eccrine glands, cutaneous sebaceous glands, glands of Zeis or glands of Moll (0/6, 0%). We also confirmed MR expression in the accessory lacrimal gland tissue. CONCLUSION: In summary, we discovered the MR receptor in the lacrimal and accessory lacrimal gland - the significance of which, in the lacrimal gland, remains unclear - but motilin may play a role in the muscarinic control of aqueous tear secretion.

Orbital emphysema following removal of bilateral midfacial implants.

A 36-year-old man with Crouzon syndrome was referred post-operatively with unilateral painful limitation of eye movements and proptosis following removal of bilateral malar and orbital rim implants. Further investigation revealed right inferior orbital emphysema, caused by the intra-operative entrance of hydrogen peroxide through a suspected perforation of the orbital septum. The symptoms settled with conservative management.

Selective embolization and resection of a large noninvoluting congenital hemangioma of the lower eyelid.

PURPOSE: To present a combined interventional radiologic and resection technique for the management of a large amblyogenic, highly vascular lesion of the lower eyelid associated with severe mechanical ectropion, conjunctival pyogenic granuloma, and recurrent, spontaneous conjunctival bleeding. METHODS: Preoperative selective embolization and coil placement were followed by resection of the tumor. RESULTS: Embolization, coil placement, and resection were uneventful with cosmetic and functional visual improvement obtained. Pathology indicated a noninvoluting congenital hemangioma. CONCLUSIONS: To the authors' knowledge, this is the first surgical technique reported in the ophthalmic literature for the selective embolization of a noninvoluting congenital hemangioma prior to its resection. Such a technique should be considered in the management of large lesions of this type.

Statins in ophthalmology.

Statins, 3-hydroxy-3-methyl-gutaryl coenzyme A reductase inhibitors, are a class of lipid-lowering drugs with anti-inflammatory, immunomodulatory, and vascular effects. Statins are increasingly being used in the treatment of a variety of medical conditions. We examine the actions of statins on the eye and its associated ophthalmic disorders. Statins can be synthetic or nonsynthetic, and their differentiating derivations may contribute to their varying cholesterol-lowering and pleiotropic effects. There is conflicting evidence on the ocular therapeutic and adverse effects of the statins. Statins may play a role in reducing the burden of dry eye, corneal ulcer scarring, thyroid-associated orbitopathy, glaucoma, uveitis and other associated ocular inflammatory states, cataract, proliferative vitreoretinopathy, diabetic retinopathy, macular degeneration, and choroidal melanoma. Topical preparations of statins can be formulated, thereby extending the range of ocular diseases that may be amenable to treatment. Statins have a relatively safe side effect profile, but rare and serious adverse reactions have been reported with their usage in ophthalmology, including myopathies and rhabdomyolysis with acute renal failure.

Necrotising anterior scleritis in a late-onset rheumatoid arthritis (LORA) patient.

Late-onset rheumatoid arthritis (LORA) is a clinically distinct entity from rheumatoid arthritis of younger onset (YORA). We present a case of necrotising anterior scleritis in an elderly lady with new-onset LORA that was initially thought to be infective. Oestrogen receptors have been identified on B cells, T cells, and macrophages with oestrogens demonstrated to increase their activation and enhance RA synovial inflammation. The presence of long-term oestrogen supplementation may have contributed to the development and perpetuation of her RA, thereby necessitating awareness of the possible immunomodulatory role of the sex steroids in immune-mediated diseases which affect the eye.

Recurrent multi-organism keratoconjunctivitis manifesting as a first presentation of common variable immune deficiency (CVID).

Common variable immune deficiency (CVID) is characterized by hypogammaglobulinemia, impaired antibody production, and recurrent bacterial infections. Reports of ocular manifestations of CVID are rare. The authors discuss a patient with recurrent keratoconjunctivitis that presented as an initial manifestation of CVID. The diagnosis of CVID should be entertained where multiple recurrences of keratoconjunctivitis are unresponsive to antibiotic and steroid therapy and when other causes of immune deficiency have been excluded. Intravenous immunoglobulin (IVIG) was used successfully as treatment and is required lifelong as prophylaxis against further episodes of keratoconjunctivitis as well as the other infectious and inflammatory complications of this primary immunodeficiency syndrome.

Multiplex cytokine detection versus ELISA for aqueous humor: IL-5, IL-10, and IFNgamma profiles in uveitis.

PURPOSE: The purpose of this study was to determine levels of IL-2, -4, -5, -10, TNF-alpha, and IFN-gamma in aqueous humor (AH) from patients with active panuveitis, anterior uveitis (AU), and noninflammatory controls by using a flow cytometric mutiplex array (CBA) and to compare with results from ELISA. METHODS: Pooled normal AH was spiked with six cytokines at decreasing concentrations for evaluating the CBA. AH was also obtained from 10 controls (cataract patients) and 36 patients with active uveitis. Cell-free supernatants were added to a cocktail of capture beads and detector antibodies or to antibody-coated wells for CBA and ELISA determination, respectively. RESULTS: CBA demonstrated greater sensitivity for detecting IL-4, IL-10, and TNF-alpha than with ELISA. Increased IFN-gamma was detected in both AU and panuveitis groups compared with controls (P < 0.01). IL-10 was higher in the panuveitis group on steroids (P < 0.01). IL-5 was detected in the control (P < 0.01) and AU groups (P < 0.05) but was undetectable in the panuveitis group (n = 10). Correlations between IFN-gamma and IL-10 were found in all uveitis groups (P < 0.01) but not in controls, whereas TNF-alpha correlations with IL-4/IFN-gamma were obtained in controls but not in the uveitis groups (P < 0.01). CONCLUSIONS: It was possible to measure cytokines titrated into normal AH specimens by CBA, and a greater number of cytokines were detected with increased sensitivity than with ELISA. Elevated IFN-gamma in active uveitis and decreased IL-5 in posterior uveitis suggest Th1 polarity is more marked, with greater uveal tract involvement. The increased IL-10 in the steroid treated group suggests glucocorticoid-induced IL-10 upregulation.

Statin Modulation of Human T-Cell Proliferation, IL-1ß and IL-17 Production, and IFN-γ T Cell Expression: Synergy with Conventional Immunosuppressive Agents.

HMG-CoA reductase inhibitors (statins) have been demonstrated to be immunomodulatory for human immune-mediated disease and in experimental models. The aim of this study was to compare statin-mediated immunosuppressive effects on human T-cell responses in vitro with those of conventional immunosuppressives (dexamethasone, cyclosporin A (CsA), mycophenolate, and rapamycin). Statins (atorvastatin, lovastatin, and simvastatin) were investigated for their modulatory effects on human PBMC viability, cytokine profiles, and T-cell proliferation. At concentrations that inhibited anti-CD3/28-stimulated T-cell proliferation (P < 0.01), simvastatin significantly decreased intracellular CD4(+) T-cell expression of IFN-γ (P < 0.01) to levels similar to those induced by conventional immunosuppressives. Atorvastatin and lovastatin also decreased IFN-γ expression, although to a lesser degree (P < 0.05). All three statins reduced levels of IL-17 production (P < 0.01). However, in response to anti-CD3/28 stimulation, simvastatin significantly upregulated IL-1ß production (P < 0.05). The profile of cytokines produced in response to anti-CD3/28 stimulation was similar when both atorvastatin and dexamethasone were added as compared with dexamethasone alone, suggesting that atorvastatin can synergise with dexamethasone with respect to immunomodulation of cytokines. This data supports the hypothesis of selective statin-mediated immunomodulatory effects on human immune cells.

Bluebottle envenomation-induced crystalline keratopathy.

PURPOSE: To report a patient who developed a crystalline keratopathy after bluebottle envenomation of the cornea. METHOD: Case report with histopathological correlation and literature review. RESULTS: A 61-year-old man presented to the Ophthalmology clinic after he was stung in the left eye by a bluebottle while swimming in the sea. He complained of ocular and facial pain, facial swelling, and transient blurred vision. First aid by the beach included a hot shower and methoxyflurane for the pain. Crystalline deposits and pseudodendritiform epithelial defects were noted on slit-lamp examination. Topical chloramphenicol was prescribed, and 2 days after the injury, the cornea was debrided of persisting crystalline material. The cornea healed quickly after debridement with visual acuity improving from 6/9 to 6/6 in the affected eye. Microscopic examination demonstrated the corneal crystals to be irregularly shaped and nonrefractile with squared off edges. Raman spectroscopy partially identified the crystals as calcium based. CONCLUSIONS: Although bluebottle stings of the cornea are infrequent, they may be challenging to manage. In addition to inactivation of the nematocysts and pain management, early debridement of the foreign matter may aid in the rapid resolution of the symptoms.

Trabeculectomy trapdoor separation with allergic periorbital dermatitis: an unusual late-onset complication of guarded filtration surgery.

Hypotony post trabeculectomy may be the result of excessive aqueous outflow. Herein a case of an elderly man with excessive filtration 2 years post trabeculectomy resulting from trapdoor separation associated with allergic periorbital dermatitis is presented. Quaternary ammonium compounds are a significant cause of allergic periorbital dermatitis. Chronic rubbing associated with allergies to multiple topical quaternary ammonium compound-containing ophthalmic preparations is likely to have contributed to the trapdoor autotrauma and separation in this man with a background of allergic contact dermatitis.

Cytokines and chemokines in uveitis: is there a correlation with clinical phenotype?

Uveitis is a general term for intraocular inflammation and includes a large number of clinical phenotypes. As a group of disorders, it is responsible for 10% of all registered blind patients under the age of 65 years. Immune-mediated uveitis may be associated with a systemic disease or may be localized to the eye. The pro-inflammatory cytokines interleukin (IL)-1beta, IL-2, IL-6, interferon-gamma and tumor necrosis factor-alpha have all been detected within the ocular fluids or tissues in the inflamed eye together with others, such as IL-4, IL-5, IL-10 and transforming growth factor-beta. The chemokines IL-8, monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and fractalkine are also thought to be involved in the associated inflammatory response. There have been a number of studies in recent years investigating cytokine profiles in different forms of uveitis with a view to determining what cytokines are important in the inflamed eye. This review attempts to present the current state of knowledge from in vitro and in vivo research on the inflammatory cytokines in intraocular inflammatory diseases.

Bilateral subacute angle-closure glaucoma in association with tonic pupils post-coronary artery bypass graft.

Anterior and posterior visual pathway disturbances have been reported post-coronary artery bypass graft surgery. Acute angle-closure glaucoma after general anaesthesia has also been well described in the literature. To date, however, there are only two cases of angle closure caused by tonic pupils. The case is reported herein of bilateral subacute angle-closure glaucoma that occurred following coronary artery bypass graft surgery in association with tonic pupils.

Churg-Strauss syndrome presenting with conjunctival nodules in association with Candida albicans and ankylosing spondylitis.

Churg-Strauss syndrome is a rare diffuse vasculitis of which the ocular manifestations have been well documented. However, reports of conjunctival involvement in Churg-Strauss syndrome are scarce. Such a presentation is described in a man with Candida albicans infection as well as ankylosing spondylitis, and a possible aetiological linkage is established amongst all three.