The relationship between inner retinal cavitation, photoreceptor disruption, and the integrity of the outer limiting membrane in macular telangiectasia type 2.

PURPOSE: The authors analyzed the relationship between the integrity of the outer limiting membrane (OLM) and the presence of inner retinal cavitation and photoreceptor disruption in eyes with macular telangiectasia Type 2 (MacTel Type 2). METHODS: Cirrus optical coherence tomography images were analyzed with attention to the presence or absence of inner and outer retinal cavities, photoreceptor loss, or disruption and OLM integrity. RESULTS: Ninety-seven eyes with MacTel Type 2 that were suitable for analysis were identified. The OLM was intact in all 48 eyes with inner retinal cavities without photoreceptor disruption. By contrast, the OLM was absent or disrupted in 8 of 10 eyes with photoreceptor disruption. CONCLUSION: If Müller cell disruption contributes to inner retinal cavitation, it does not appear to affect the OLM, which is the only part of the Müller cell that is visible clinically. By contrast, the integrity of both the OLM and photoreceptors appear to be closely linked in MacTel Type 2. This observation is consistent with the hypothesis that Müller cell dysfunction plays a role in the pathogenesis of MacTel.

Small cell neuroendocrine carcinoma masquerading as cellulitis and causing blindness via bilateral orbital involvement.

CASE REPORT: We report the first case of small cell neuroendocrine carcinoma involving both orbits and causing complete blindness. The patient was initially prescribed antibiotics for right periorbital cellulitis, but magnetic resonance imaging demonstrated abnormal enhancing tissue in the superomedial and superior right orbit with destruction of the anterior lamina papyracea, extension into the anterior ethmoid air cells, further extension into the right frontal bone and pockets of fluid in the right frontal lobe. Histopathology from the orbital tissue and right frontal subdural empyema demonstrated small cell neuroendocrine carcinoma of 'small blue cell' subtype. The patient received multidisciplinary treatment combining surgery, chemotherapy (both systemic and intra-arterial) and radiotherapy but passed away in the second year of treatment. COMMENT: Primary small cell neuroendocrine carcinoma is an extremely rare tumour, most frequently occurring in the lungs. An understanding of the pathology has been difficult, due to its rarity and the complexity of the histological diagnosis. Neuroendocrine carcinoma has a very poor prognosis and further research is required for more effective treatment options.

Digital eye drop instillation--a novel method.

BACKGROUND: Local drug treatment in ophthalmology by the use of eye drops has meant that potent drugs can be used, thereby minimising systemic side effects. While seemingly a simple task, insertion of eye drops can be problematic for certain patients and in particular circumstances. OBJECTIVE: To describe a novel method for the administration of eye drops, which overcomes the main problems of conventional eye drop administration. DISCUSSION: Our pragmatic method of eye drop application provides a way of improving compliance and reducing ocular surface injury. Our experience to date is that the technique is at least as safe as that used for insertion of contact lenses from an infection risk perspective.

The gut microbiome and primary open angle glaucoma: Evidence for a 'gut-glaucoma' axis?

Glaucoma presents an epidemiological burden as the leading cause of irreversible blindness globally and the most common cause of preventable blindness. While elevated intraocular pressure is the strongest modifiable risk factor, the exact mechanisms of retinal ganglion cell damage leading to progressive vision loss are not entirely understood. Studies of other neurodegenerative diseases show a potential for human gut microbiome dysbiosis to play a pathogenic role. An investigation into whether the microbiome, a potential modifiable risk factor, has significance in glaucoma enables exploration of prophylactic or additive treatments. Elevated population levels of specific bacterial species have been noted in glaucoma patients, particularly Prevotellaceae, Enterobacteriaceae and Escherichia coli, while Megomonas is speculated to be protective. Evidence also points to systemic neuro-inflammation and disruption of autoimmune processes as a result of imbalances in both human and animal models, where heat shock proteins may contribute to pathogenesis. Further research into the influence of gut microbiome on pathogenesis offers a chance to minimise irreversible vision loss in glaucoma.

Treatment of conjunctival and corneal epithelial neoplasia with retinoic acid and topical interferon alfa-2b: long-term follow-up.

OBJECTIVE: To evaluate the long-term recurrence rate of conjunctival and corneal intraepithelial neoplasia (CIN) treated with retinoic acid and topical interferon alfa-2b. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: A total of 89 eyes of 89 patients from 1 institution who were treated between September 2003 and February 2010 for CIN lesions used topical interferon alfa 1 million IU/ml drops 4 times daily and retinoic acid 0.01% once every second day. METHODS: Diagnosis was made by biopsy and impression cytology. Patients' notes and clinical photographs were reviewed, and data were analyzed. All eyes were monitored for the possibility of recurrence with a minimum of 1 year of follow-up from the time of documented clinical resolution. MAIN OUTCOME MEASURES: All eyes were monitored for the possibility of recurrence with a minimum of 1 year of follow-up from the time of documented clinical resolution. RESULTS: Complete clinical resolution of the CIN lesions was achieved in 87 of the 89 eyes treated (97.75%). Two of the 89 eyes treated (2.25%) had only a partial response to treatment; of these 2 patients, 1 was taking cyclosporine for keratitis sicca. For the 87 eyes with complete response, resolution occurred after a mean of 1.69 months (range, 19 days to 6.5 months). Mean follow-up after clinical resolution (tumor-free period) was 51.5 months (range, 11-84 months). Four of the 87 patients with complete response developed a mild allergic papillary conjunctivitis that settled on halving the interferon dose to 0.5 million IU drops and reducing the frequency to 3 times daily. Side effects were limited to 1 case of epithelial microcysts and 1 case of marginal keratitis. CONCLUSIONS: In this group of patients observed with CIN lesions, combination treatment of topical retinoic acid and interferon alfa-2b was effective in treating lesions with minimal self-limited side effects with faster and greater resolution and a longer tumor-free period compared with studies using interferon alfa-2b alone. We hypothesize that topical all-trans retinoic acid and interferon alfa-2b may act synergistically. We believe that combination treatment of interferon alfa-2b and retinoic acid may offer a superior alternative to interferon alfa-2b alone in treating CIN.

Cytophagic histiocytic panniculitis with haemophagocytosis in a patient with familial multiple lipomatosis and review of the literature.

We report a patient with the extremely rare familial multiple lipomatosis syndrome, who developed the uncommon autoimmune disease cytophagic histiocytic panniculitis, manifested as inflammation of preexisting lipomas. Despite his initial critical condition and unsuccessful treatment with steroids, he responded to cyclosporin and remains well 15 years after diagnosis. In contrast with most previous reports, our patient stays dependent on cyclosporin; repeated attempts of discontinuing or substituting treatment were quickly followed by relapse. Haemophagocytic panniculitis is considered as a T-cell disorder, but its exact pathophysiological mechanism has not been clarified. Differential diagnosis of cytophagic histiocytic panniculitis mainly includes malignant histiocytosis, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus panniculitis (lupus profundus). We discuss the main clinical features, diagnostic challenges and treatment issues of this usually benign, but at times life-threatening autoimmune condition.

Refractory iatrogenic pigmentary glaucoma secondary to cosmetic laser treatment: A case report.

PURPOSE: To report a case of bilateral iatrogenic pigmentary glaucoma secondary to cosmetic iris-lightening laser treatment. CASE REPORT: A 39-year-old patient presented with bilateral iatrogenic pigmentary glaucoma. She had elevated intraocular pressures (IOPs), scattered iris pitting, and intense angle pigmentation secondary to the cosmetic laser treatment she underwent 4 weeks prior to presentation. Her IOPs were refractory to maximal medical treatment and she subsequently underwent trabeculectomy. CONCLUSION: The true scale of complications related to cosmetic laser treatments is as yet unknown. Robust clinical investigations into its safety profile, including long-term data, are required. Prospective patients should consider this with great care. Clinicians should be aware of the potential risks of this procedure, as early recognition of cosmetic laser-induced pigmentary glaucoma may avert further sequelae.

Dual roles of different redox forms of complement factor H in protecting against age related macular degeneration.

Complement Factor H (CFH) is an important inhibitor of the alternate complement pathway in Bruch's membrane (BM), located between the choriocapillaris and the retinal pigment epithelium. Furthermore dysfunction of its activity as occurs with certain polymorphisms is associated with an increased risk of age related macular degeneration (AMD). The retina is a site of high generation of reactive oxygen species (ROS) and dysfunction of redox homeostasis in this milieu also contributes to AMD pathogenesis. In this study we wanted to explore if CFH exists in distinct redox forms and whether these species have unique protective biological functions. CFH can be reduced by the naturally occurring thioredoxin - 1 in CFH domains 1-4, 17-20. We found a duality of function between the oxidised and reduced forms of CFH. The oxidised form was more efficient in binding to C3b and lipid peroxidation by-products that are known to accumulate in the retinae and activate the alternate complement pathway. Oxidised CFH enhances Factor I mediated cleavage of C3 and C3b whereas the reduced form loses this activity. In the setting of oxidative stress (hydrogen peroxide)-mediated death of human retinal pigment epithelial cells as can occur in AMD, the free thiol form of CFH offers a protective function compared to the oxidised form. We found for the first time using a novel ELISA system we have developed for free thiol CFH, that both redox forms of CFH are found in the human plasma. Furthermore there is a distinct ratio of these redox forms in plasma depending if an individual has early or late AMD, with individuals with early AMD having higher levels of the free thiol form compared to late AMD.

Nitration of tyrosines in complement factor H domains alters its immunological activity and mediates a pathogenic role in age related macular degeneration.

Nitrosative stress has been implicated in the pathogenesis of age related macular degeneration (AMD). Tyrosine nitration is a unique type of post translational modification that occurs in the setting of inflammation and nitrosative stress. To date, the significance and functional implications of tyrosine nitration of complement factor H (CFH), a key complement regulator in the eye has not been explored, and is examined in this study in the context of AMD pathogenesis.Sections of eyes from deceased individuals with AMD (n = 5) demonstrated the presence of immunoreactive nitrotyrosine CFH. We purified nitrated CFH from retinae from 2 AMD patients. Mass spectrometry of CFH isolated from AMD eyes revealed nitrated residues in domains critical for binding to heparan sulphate glycosaminoglycans (GAGs), lipid peroxidation by-products and complement (C) 3b.Functional studies revealed that nitrated CFH did not bind to lipid peroxidation products, nor to the GAG of perlecan nor to C3b. There was loss of cofactor activity for Factor I mediated cleavage of C3b with nitrated CFH compared to non-nitrated CFH. CFH inhibits, but nitrated CFH significantly potentiates, the secretion of the pro-inflammatory and angiogenic cytokine IL-8 from monocytes that have been stimulated with lipid peroxidation by-products. AMD patients (n = 30) and controls (n = 30) were used to measure plasma nitrated CFH using a novel ELISA. AMD patients had significantly elevated nitrated CFH levels compared to controls (p = 0.0117). These findings strongly suggest that nitrated CFH contributes to AMD progression, and is a target for therapeutic intervention.

Do Beta 2-Glycoprotein I Disulfide Bonds Protect the Human Retina in the Setting of Age-Related Macular Degeneration?

Age-related macular degeneration (AMD) affects the region of the retina that is responsible for high-resolution vision. It is a major cause of blindness in the aging population. This is the first study that examines the association of redox-modified, cysteine-based, post-translational forms of beta 2-glycoprotein I (ß2GPI) in the plasma of individuals with early and late stages of patients with AMD compared with controls. Exploration is also undertaken to assess whether the free thiol form of ß2GPI versus the oxidized disulfide form have distinct functional properties in the setting of hydrogen peroxide (H(2)O(2))-mediated cell death of an immortalized human retinal pigment epithelium (RPE) cell line. We demonstrate ß2GPI in the retina and choroid of patients with AMD. Free thiol ß2GPI is shown to protect the immortalized human RPE cell line against H(2)O(2)-induced cell death, whereas the oxidized form of ß2GPI and free thiol bovine serum albumin were not protective. Free thiol ß2GPI levels were significantly decreased in patients with late AMD compared with early AMD and healthy controls. Our observations lead to the hypothesis that free thiol ß2GPI may protect against oxidative stress injury to RPE cells in the early stages of AMD.

'Popper'-induced vision loss.

Amyl nitrite 'poppers' are recreational drugs, which are a potent source of nitric oxide. The use of 'poppers' can cause psychoactive stimulation, reduced blood pressure, tachycardia and involuntary muscle relaxation. Their use is becoming increasingly common around the world, including approximately 60% of Australia's male homosexual community. We report the first case of 'popper'-induced vision loss in Australasia.

Vision loss and partial third nerve palsy following contralateral peribulbar anesthesia.

We report the case of a 72-year-old woman who experienced transient complete visual loss and a partial third nerve palsy in 1 eye following cataract surgery under local anesthesia in the fellow eye. Symptoms and signs were determined to result from the administration of a peribulbar block, which was presumably associated with ipsilateral transoptic nerve sheath spread. We believe this is the first report of contralateral amaurosis and oculomotor nerve palsy following peribulbar anesthesia.

Squash(ed): Craniofacial and vertebral injury from collision on squash court.

Squash is a popular racquet sport not usually associated with severe head or spinal injury. The incidence of squash-related injury ranges from 35.5 to 80.9 per 100,000 players, with the most common sites being the lower-limbs and eyes. We present a case of extensive traumatic craniomaxillofacial and vertebral injury resulting from collision on a squash court, without use of protective gear. The patient sustained fractures of the frontal bone, orbits, maxillae, zygomas, the first and second cervical vertebrae and the spinous process of the seventh cervical vertrebra. This is the first case of squash-related injury with such extensive craniofacial and vertebral involvement. This unique case required multiple surgical procedures as well as an extensive admission to the intensive care unit and highlights the risk of significant craniomaxillofacial trauma in sports not usually associated with such injuries.