Nathan M. Kerr

Toward zero effective phacoemulsification time using femtosecond laser pretreatment.

OBJECTIVE To compare effective phacoemulsification time after femtosecond laser pretreatment with conventional phacoemulsification and the associated effect on visual outcomes and endothelial cell loss. DESIGN Prospective, consecutive, single-surgeon case-control study. CONTROLS Controls underwent phacoemulsification cataract extraction plus insertion of an intraocular lens (IOL). Cases underwent pretreatment with the femtosecond laser followed by phacoemulsification cataract extraction and IOL insertion. METHODS Two hundred one eyes underwent cataract surgery between April 2012 and July 2012. Data collected included patient demographics, preoperative characteristics, femtosecond lens fragmentation method, effective phacoemulsification time (EPT), intraoperative complications, and postoperative outcomes. MAIN OUTCOME MEASURES Effective phacoemulsification time, intraoperative complications, corneal endothelial cell loss, as well as postoperative best-corrected visual acuity, intraocular pressure, and refractive outcomes. RESULTS Patient demographics were similar between groups. There was no difference between baseline cataract grades (2.59 ± 0.71 vs. 2.52 ± 0.72, not significant). One hundred percent of cases pretreated with the femtosecond laser had complete capsulotomy. Mean EPT was reduced by 83.6% in the femtosecond pretreatment group (P<0.0001) when compared with controls, with 30% having 0 EPT (P<0.0001). Effective phacoemulsification time was reduced 28.6% within the femtosecond group using improved lens fragmentation algorithms, and a further 72.8% reduction was achieved with a 20-gauge phacoemulsification tip. Overall, there was a 96.2% reduction in EPT between controls and the optimized femtosecond pretreatment group. This was associated with a 36.1% reduction in endothelial cell loss in the femtosecond group. Visual and refractive outcomes were similar to those of conventional cataract surgery. CONCLUSIONS Femtosecond laser pretreatment results in a significant reduction in effective phacoemulsification time, including the possibility of 0 EPT. Further reductions may be achieved using optimization of lens fragmentation patterns and surgical technique. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Connexin43 mimetic peptide reduces vascular leak and retinal ganglion cell death following retinal ischaemia

Connexin43 gap junction protein is expressed in astrocytes and the vascular endothelium in the central nervous system. It is upregulated following central nervous system injury and is recognized as playing an important role in modulating the extent of damage. Studies that have transiently blocked connexin43 in spinal cord injury and central nervous system epileptic models have reported neuronal rescue. The purpose of this study was to investigate neuronal rescue following retinal ischaemia-reperfusion by transiently blocking connexin43 activity using a connexin43 mimetic peptide. A further aim was to evaluate the effect of transiently blocking connexin43 on vascular permeability as this is known to increase following central nervous system ischaemia. Adult male Wistar rats were exposed to 60 min of retinal ischaemia. Treatment groups consisted of no treatment, connexin43 mimetic peptide and scrambled peptide. Retinas were then evaluated at 1-2, 4, 8 and 24 h, and 7 and 21 days post-ischaemia. Evans blue dye leak from retinal blood vessels was used to assess vascular leakage. Blood vessel integrity was examined using isolectin-B4 labelling. Connexin43 levels and astrocyte activation (glial fibrillary acidic protein) were assessed using immunohistochemistry and western blot analysis. Retinal whole mounts and retinal ganglion cell counts were used to quantify neurodegeneration. An in vitro cell culture model of endothelial cell ischaemia was used to assess the effect of connexin43 mimetic peptide on endothelial cell survival and connexin43 hemichannel opening using propidium iodide dye uptake. We found that retinal ischaemia-reperfusion induced significant vascular leakage and disruption at 1-2, 4 and 24 h following injury with a peak at 4 h. Connexin43 immunoreactivity was significantly increased at 1-2, 4, 8 and 24 h post ischaemia-reperfusion injury co-localizing with activated astrocytes, Muller cells and vascular endothelial cells. Connexin43 mimetic peptide significantly reduced dye leak at 4 and 24 h. In vitro studies on endothelial cells demonstrate that endothelial cell death following hypoxia can be mediated directly by opening of connexin43 hemichannels in endothelial cells. Blocking connexin43 mediated vascular leakage using a connexin43 mimetic peptide led to increased retinal ganglion cell survival at 7 and 21 days to levels of uninjured retinas. Treatment with scrambled peptide did not result in retinal ganglion cell rescue. Pharmacological targeting of connexin43 gap junction protein by transiently blocking gap junction hemichannels following injury provides new opportunities for treatment of central nervous system ischaemia.

Non-arteritic anterior ischaemic optic neuropathy: A review and update

Non-arteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy in people aged 50 years and older. The condition is caused by infarction of the laminar or retrolaminar portion of the optic nerve head supplied by the short posterior ciliary arteries (SPCAs). The underlying aetiology and pathophysiology is poorly elucidated. Factors that have been implicated include nocturnal hypotension, impaired autoregulation of the microvascular supply, vasculopathic occlusion, and venous insufficiency. These factors are thought to result in axonal oedema causing a compartment syndrome in a structurally crowded optic disc leading to axonal degeneration and loss of retinal ganglion cells via apoptosis. Clinically NAION is characterised by sudden, usually painless, loss of vision in one or both eyes. Examination findings include decreased visual acuity, a visual field defect, decreased colour vision, a relative afferent pupillary defect, and optic disc swelling. Despite significant research, treatment options for NAION remain limited.

Femtosecond laser-assisted cataract surgery compared with conventional cataract surgery.

Background To investigate the safety and efficacy of the Catalys (Optimedica, Santa Clara, CA, USA) femtosecond laser-assisted cataract surgery system compared with conventional phacoemulsification cataract extraction. Design Prospective, consecutive, parallel cohort study. Participants The first 200 eyes undergoing conventional cataract surgery to the first 200 eyes undergoing femtosecond laser-assisted cataract surgery between April and July 2012. Methods Femtosecond laser-assisted cataract surgery involved anterior capsulotomy and lens fragmentation based on optical coherence tomography-guided treatment mapping. Conventional cataract surgery involved manual continuous curvilinear capsulorhexis. Both procedures were completed by standard phacoemulsification and insertion of an intraocular lens. Main Outcome Measures Effective phacoemulsification time and intraoperative complication rates. Results Patient demographics were similar between both groups. There was no statistically significant difference in intraoperative complications between femtosecond laser-assisted cataract surgery and conventional surgery. There was one posterior capsule rupture in both groups (0.5%; not significant). One hundred per cent of cases treated with the femtosecond laser had a complete capsulotomy. Vacuum time decreased with experience. Effective phacoemulsification time was reduced by 70% in the femtosecond group (P < 0.0001). Twenty-six cases in the femtosecond group versus one case in the conventional group had 0 effective phacoemulsification time (P < 0.0001). Conclusion Femtosecond laser-assisted cataract surgery appears to be as safe as conventional cataract surgery in the short term and results in significantly lower effective phacoemulsification time. Although it may allow for greater efficiency and decreased postoperative complications, further research is needed into long-term safety aspects such as corneal endothelial cell loss.To investigate the safety and efficacy of the Catalys (Optimedica, Santa Clara, CA, USA) femtosecond laser‐assisted cataract surgery system compared with conventional phacoemulsification cataract extraction.

Intravitreal injections: is there benefit for a theatre setting?

Objective To investigate and compare the rate of endophthalmitis after intravitreal injections performed in an in-office (dedicated procedure room) versus in-theatre setting. Methods A retrospective comparative cohort study was performed of all patients consecutively treated by a single surgeon with intravitreal injection with either ranibizimab or bevacizumab for any recognised clinical indication. All cases received injections between March 2006 and March 2012, during which time all injections were prospectively recorded on an electronic medical record system. A search of the electronic database using a report building system was used to extract the total number of injections into location-specific grouping (ie, in office vs in theatre). Results 12 249 injections were performed over a 6-year period. 3376 of these were performed in the in-office procedure room, compared with 8873 in the operating theatre. Of the 3376 injections performed in office, there were four cases of infective endophthalmitis compared with none of the 8873 injections performed in theatre (p=0.006). In-theatre intravitreal injections were associated with a 13-fold lower risk of endophthalmitis compared to in-office injections. Conclusions The theatre environment is a clinically appropriate location for any intravitreal injection procedures and was associated with a significantly lower risk of infective endophthalmitis in this single-surgeon comparative cohort study.

Diagnostic accuracy of confrontation visual field tests

Objective: To determine the diagnostic accuracy of confrontation visual field testing and to compare the accuracy of confrontation tests both individually and in combination. Methods: Patients were prospectively recruited from ophthalmology clinics over a 6-month period. All patients underwent SITA-standard 24–2 Humphrey visual field analysis. Two examiners, masked to the automated perimetry results and the results of the other examiner, assessed patients using 7 common confrontation visual field tests. The order of testing was randomized to reduce any learning effect. For each individual test and combination of tests, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results: A total of 301 eyes from 163 patients were included in the study. The average mean deviation was −5.91 ± 7.72 (SD) dB. Most confrontation tests were insensitive to the identification of field loss. The sensitivity and specificity varied depending on the type, density, and cause of the visual field defect. Kinetic testing with a red target provided the highest sensitivity (74.4%) and specificity (93.0%) of any individual test and when combined with static finger wiggle testing achieved a sensitivity of 78.3% while retaining a specificity of 90.1%. Conclusions: Confrontation visual field tests are insensitive at detecting visual field loss when performed individually and are therefore a poor screening test. Combining confrontation tests is a simple and practical method of improving the sensitivity of confrontation testing.

Immunolocalization of Gap Junction Protein Connexin43 (GJA1) in the Human Retina and Optic Nerve

PURPOSE Gap junctions are intercellular channels that have been implicated in the pathogenesis of neuronal death after central nervous system injury. This study determines the expression pattern of gap junction protein connexin43 in the human retina and optic nerve. METHODS An affinity-isolated polyclonal antibody to the C-terminal segment of the cytoplasmic domain of human connexin43 was used to determine connexin43 localization. Postmortem human eyes were examined by immunohistochemical staining of frozen sections using antibodies to connexin43. Antibody binding was detected using confocal microscopy and fluorochrome-conjugated secondary antibodies. Double-label immunohistochemistry identified the cell types expressing connexin43. RESULTS Connexin43 immunoreactivity was detected in the human retina on glial fibrillary acidic protein (GFAP)-positive astrocytes in the retinal ganglion cell layer and, to a lesser extent, on the processes of glutamine synthetase-labeled Müller cells. The retinal and choroidal circulations showed strong connexin43 immunolabeling. Dense connexin43 immunoreactivity was present between adjacent cells of the retinal pigment epithelium, and there was diffuse connexin43 immunoreactivity on GFAP-positive astrocytes in the optic nerve. CONCLUSIONS In the human retina and optic nerve, connexin43 is present on glia, blood vessels, and epithelial cells. An understanding of the distribution of connexin43 in the normal retina and optic nerve may be used to evaluate changes associated with retinal and optic nerve disease.

Giant cell arteritis

Giant cell arteritis (GCA) is an immune-mediated vasculitis affecting individuals over 50 years of age. It is characterised by granulomatous inflammation that affects medium-sized and large arteries. The wide spectrum of clinical manifestations can be divided into those related to tissue ischemia from vascular lesions and those related to a systemic inflammatory response. The pathogenesis of these groups also appears distinct, with vascular lesion formation thought to be an adaptive immune response, and the systemic inflammatory reaction an innate immune response. Clinical suspicion of GCA must remain especially high in those with neurological or visual symptoms and if warranted, prompt treatment with high-dose corticosteroids is invaluable in halting disease progression.

Phosphodiesterase inhibitors and the eye

Phosphodiesterase type 5 (PDE5) inhibitors are effective oral treatments for erectile dysfunction and have become one of the most widely prescribed medications worldwide. The mechanism of action is to reduce the degradation of cyclic GMP (cGMP) potentiating the effect of nitric oxide in the corpus cavernosum and allowing erectile function to occur by consequent relaxation of penile smooth muscle. Because of the presence of PDE5 in choroidal and retinal vessels these medications increase choroidal blood flow and cause vasodilation of the retinal vasculature. The most common symptoms are a blue tinge to vision and an increased sensitivity to light. There have been reports of non‐arteritic anterior ischaemic optic neuropathy and serous macular detachment in users of PDE5 inhibitors, although a causal relationship has not been conclusively shown. Despite the role of cGMP in the production and drainage of aqueous humour these medications do not appear to alter intraocular pressure and are safe in patients with glaucoma. All PDE5 inhibitors weakly inhibit PDE6 located in rod and cone photoreceptors resulting in mild and transient visual symptoms that correlate with plasma concentrations. Psychophysical tests reveal no effect on visual acuity, visual fields or contrast sensitivity; however, some studies show a mild and reversible impairment of blue‐green colour discrimination. PDE5 inhibitors transiently alter retinal function on electroretinogram testing but do not appear to be retinotoxic. Despite the role of cyclic nucleotides in tear production there is no detrimental effect on tear film quality. Based on the available evidence PDE5 inhibitors have a good ocular safety profile.

High pressure-induced retinal ischaemia reperfusion causes upregulation of gap junction protein connexin43 prior to retinal ganglion cell loss.

We aimed to characterise the spatial and temporal expression of connexin43 (Cx43) following retinal ischaemia-reperfusion injury and to evaluate its relationship to retinal glial response and subsequent retinal ganglion cell loss. Unilateral retinal ischaemia-reperfusion injury was induced by elevating intraocular pressure to 120mmHg for 60 min and then normalized in Wistar rats. Retinas (n=110) were evaluated at 4, 8, and 24h, and 7, 14, and 21 days in 4 groups: ischaemic, contralateral, sham operated, and uninjured eyes. Immunohistochemistry was used to analyse the spatial and cell-specific expression of Cx43 protein, glial fibrillary acidic protein (astrocytes), glutamine synthetase (Muller cells), Isolectin B4 (vascular endothelium), DAPI (nuclear marker), and BRN3a (retinal ganglion cells). Retinal whole mounts were used to count retinal ganglion cells. Our results show that Cx43 immunoreactivity of the ischaemic eye is significantly increased in the ganglion cell layer and nerve fibre layer, colocalizing with activated retinal astrocytes and Muller cells at 8h. In the inner retinal layers Cx43 was also upregulated and colocalized with retinal vascular endothelium at 4, 8 and 24h post ischaemia. Notably, in the contralateral eye, Cx43 immunoreactivity was also significantly increased in the ganglion cell layer and nerve fibre layer at 8 and 24h, and at 4h in the inner layers. Sham operated controls did not show any change in Cx43 immunoreactivity. Subsequently a significant retinal ganglion cell loss was observed in the ischaemic eye at day 21 with a trend towards retinal ganglion cell loss in the contralateral eye. In conclusion, upregulation of Cx43 occurs in both the ischaemic and contralateral retinas although far more significantly in injured retinas. Cx43 colocalizes primarily with activated retinal astrocytes and Muller cells as well as vascular endothelium, suggesting that gap junction communication and/or hemichannel activity may be a mediator of inflammation, vascular permeability, and subsequently neuronal death.