Prospective one year study of corneal biomechanical changes following high intensity, accelerated cornea cross-linking in patients with keratoconus using a non-contact tonometer.

PURPOSE: To characterize corneal biomechanical properties utilizing a dynamic ultra-high-speed Scheimpflug camera equipped with a non-contact tonometer (CorVis ST, CST) in keratoconic corneas following continuous high intensity, high irradiance corneal cross-linking. DESIGN: Prospective longitudinal single-centre study at a tertiary referral center. METHODS: Corneal biomechanical properties were measured in patients with progressive keratoconus undergoing high intensity (30 mW/cm2), high irradiance (5.4 J/cm2), accelerated corneal cross-linking with continuous exposure to ultraviolet-A for 4 min. CST was used to assess corneal biomechanical properties pre-operatively and at 1, 3, 6 and 12 months post-operatively. CST output videos were further analyzed using several previously reported algorithms. RESULTS: A total of 25 eyes of 25 participants were examined. The mean age of participants was 20.9 ± 5.3 years; 56% were male and 80% were of Maori or Pacific Island origin. Energy absorbed area (mN mm), was the only significantly changed parameter compared to baseline at all time points measuring 3.61 ± 1.19 preoperatively, 2.81 ± 1.15 at 1 month (p = 0.037), 2.79 ± 0.81 (p = 0.033) at 3 months, 2.76 ± 0.95 (p = 0.028) at 6 months and 2.71 ± 1.18 (p = 0.016) at 12 months. CONCLUSIONS: The significant difference between the pre and post-operative energy absorbed area appears to reflect changes in corneal viscous properties that occur following corneal cross-linking.

Association of Nailfold Capillary Abnormalities With Primary Open-angle Glaucoma and Glaucomatous Visual Field Loss.

PRECIS: Nailfold capillary abnormalities are associated with primary open-angle glaucoma (POAG) and increased severity of global and central glaucomatous visual field (VF) loss. PURPOSE: The purpose of this study was to investigate whether nailfold capillary abnormalities are associated with POAG and the severity of glaucomatous VF loss. MATERIALS AND METHODS: A cross-sectional study of 83 POAG cases and 40 controls was conducted. Nailfold capillaroscopy images were assessed by masked graders for dilated capillaries >50 µm, crossed capillaries, tortuous capillaries, hemorrhages, avascular zones >100 µm, capillary density, and capillary distribution. VF loss in glaucoma cases was quantified using mean deviation and mean central pattern standard deviation (PSD) from the worst-affected eye. RESULTS: Logistic regression analyses of cases and controls showed that avascular zones [odds ratio (OR)=1.24; 95% confidence interval (CI): 1.06, 1.47; P=0.005], capillary density (OR=0.63; 95% CI: 0.46, 0.83; P<0.001), and capillary distribution (OR=7.88; 95% 95% CI: 2.53, 28.40; P=0.001) were associated with POAG. Simple linear regression analysis of cases only showed that nailfold hemorrhages were associated with mean deviation (ß=-5.10; 95% CI: -9.20, -1.01; P=0.015) and mean central PSD (ß=-4.37; 95% CI: -8.18, -0.57; P=0.025), and this remained significant in the multiple linear regressions. After controlling for demographic and clinical factors, avascular zones were associated with both mean deviation (ß=-0.76; 95% CI: -1.48, -0.04; P=0.040) and mean central PSD (ß=-0.78; 95% CI: -1.45, -0.10; P=0.024), whereas capillary distribution was only associated with mean deviation (ß=-4.67; 95% CI: -7.92, -1.43; P=0.017). CONCLUSION: Nailfold capillary abnormalities are associated with POAG as well as increased global and central vision loss.

Visual loss and recovery in chiasmal compression.

Compression of the optic chiasm causes an optic neuropathy that may be associated with reversible visual loss often immediately following surgical decompression. While the precise pathogenesis of retinal ganglion cell impairment and eventual death remains poorly understood, a number of putative mechanisms may play a role. In this article we review the evidence supporting various stages of visual loss and recovery in chiasmal compression. These include conduction block, demyelination, ischemic insult, and retrograde and anterograde degeneration. We also describe novel advances in magnetic resonance imaging with specialized modalities such as diffusion tensor imaging have provided further information to explain the underlying mechanism of visual loss. Functional measures including electrophysiology are time-consuming but have shown moderate prognostic ability. Optical coherence tomography has provided novel new biomarkers for predicting outcome following surgical decompression. Both retinal nerve fiber layer thickness and ganglion cell complex thicknesses have shown to have excellent predictive power. Such advances serve to inform patients and clinicians of pre-operative factors that predict the extent of visual recovery following medical or surgical treatment of para-chiasmal lesions.

Caffeine and the eye.

Caffeine, a popular psychostimulant that acts as an adenosine receptor antagonist, is the most widely used drug in history, consumed daily by people worldwide. Knowledge of the physiological and pathological effects of caffeine is crucial in improving public health because of its widespread use. We provide a summary of the current evidence on the effect of caffeine on the eye. Most of the research conducted to date is in relation to cataract and glaucoma, two of the most common eye diseases among the elderly.

Demographics and ocular biometric characteristics of patients undergoing cataract surgery in Auckland, New Zealand.

BACKGROUND: The aim is to investigate ethnic variation, in presentation and biometric parameters, within the population undergoing cataract surgery in Auckland. DESIGN: The design is a retrospective study. PARTICIPANTS: Four thousand nine hundred thirty-one eyes of 3524 consecutive patients undergoing cataract surgery in Auckland Public Hospital over 18 months were included in the study. METHODS: Analysis of preoperative medical records was performed. MAIN OUTCOME MEASURES: Age, gender, self-reported ethnicity, keratometry, anterior chamber depth, axial length and intraocular lens (IOL) power data were collected. RESULTS: Maori (4.7%) were under-represented compared with the proportion of Maori attending the eye clinic (5.5%) and in the major patient catchment area (8.2%). People of Maori, Pacific and Indian ethnicities presented at a significantly younger age (66.4, 65.9 and 67.9 years, respectively) than those of Caucasian and Asian ethnicities (76.4 and 71.3 years, respectively, P < 0.001). Advanced cataract was more likely in Pacific peoples and Maori than Caucasians. The mean axial length was longest in Asian eyes (23.83 ± 1.52 mm). The mean anterior chamber depth in the eyes of Pacific peoples (3.20 ± 0.39 mm) was significantly greater than that of Caucasians (3.09 ± 0.42 mm, P = 0.001) and Asians (3.05 ± 0.49 mm, P < 0.001). The mean IOL power in Asian eyes was 19.45D. This was significantly lower than the IOL power required by Caucasian (20.72D, P < 0.001) and Pacific ethnicities (20.61D, P = 0.001). With-the-rule astigmatism was highly prevalent in Maori and Pacific peoples, whereas in all other ethnicities, against-the-rule astigmatism was more common. CONCLUSIONS: This study identified significant ethnic variation in presentation for cataract surgery and ocular biometric parameters. These data may help identify potential biometric refinements and those at risk of developing ocular morbidities known to be associated with these parameters.

Sphere-forming cells from peripheral cornea demonstrate a wound-healing response to injury.

The cornea is the initial refractive interface of the eye. Its transparency is critical for clear vision and is maintained by stem cells which also act to repair injury inflicted by external insults, such as chemical and thermal burns. Damage to the epithelium compromises its clarity and can reduce or eliminate the stem cell population, diminishing the ability for self-repair. This condition has been termed "limbal stem cell deficiency"; severe cases can lead to corneal blindness. Sphere-forming cells isolated from peripheral cornea are a potential source of stem and progenitor cells for corneal repair. When provided with appropriate substrate, these spheres have the ability to adhere and for cells to migrate outwards akin to that of their natural environment. Direct compression injury and remote scratch injury experiments were conducted on the sphere cells to gauge their wound healing capacity. Measures of proliferation, differentiation, and migration were assessed by immunohistochemical detection of EdU incorporation, α-smooth muscle actin expression and confocal image analysis, respectively. Both modes of injury were observed to draw responses from the spheres indicating wound healing processes. Direct wounding induced a rapid, but transient increase in expression of α-SMA, a marker of corneal myofibroblasts, followed by a proliferative and increasing migratory response. The spheres were observed to respond to remote injury as entire units, with no directional response seen for targeted repair over the scratch injury area. These results give strength to the future use of these peripheral corneal spheres as transplantable units for the regeneration of corneal tissue.

Limbal stem cells: Central concepts of corneal epithelial homeostasis.

A strong cohort of evidence exists that supports the localisation of corneal stem cells at the limbus. The distinguishing characteristics of limbal cells as stem cells include slow cycling properties, high proliferative potential when required, clonogenicity, absence of differentiation marker expression coupled with positive expression of progenitor markers, multipotency, centripetal migration, requirement for a distinct niche environment and the ability of transplanted limbal cells to regenerate the entire corneal epithelium. The existence of limbal stem cells supports the prevailing theory of corneal homeostasis, known as the XYZ hypothesis where X represents proliferation and stratification of limbal basal cells, Y centripetal migration of basal cells and Z desquamation of superficial cells. To maintain the mass of cornea, the sum of X and Y must equal Z and very elegant cell tracking experiments provide strong evidence in support of this theory. However, several recent studies have suggested the existence of oligopotent stem cells capable of corneal maintenance outside of the limbus. This review presents a summary of data which led to the current concepts of corneal epithelial homeostasis and discusses areas of controversy surrounding the existence of a secondary stem cell reservoir on the corneal surface.

Effect of low Mg2+ and bicuculline on cell survival in hippocampal slice cultures.

A reliable model system of epileptiform insult would facilitate investigation into the underlying biological mechanisms. Epileptiform insult was induced in hippocampal slice cultures by lowering extracellular Mg(2+), (+)-bicuculline, or (-)-bicuculline methochloride, a stable salt form of bicuculline (both forms block GABA(A) receptors). Cell death was assessed by propidium iodide uptake. Low Mg(2+) or (+)-bicuculline did not produce cell death regardless of dose or incubation period. Exposure to 100 microM (-)-bicuculline methochloride for 48 hr resulted in prominent CA1 cell death. These findings demonstrate that not all pro-epileptic drugs/ion changes used routinely for electrophysiological recording of seizure activity lead to cell death in hippocampal slice cultures and that treatment with bicuculline methochloride can be used as a reliable model for epileptiform insult.

Dose-dependent protective effect of connexin43 mimetic peptide against neurodegeneration in an ex vivo model of epileptiform lesion.

Epileptic seizures typically result in delayed neuronal loss secondary to the initial damage and an up-regulation in connexin43 (Cx43). This study investigated the role of Cx43 gap junctions in lesion spread and cell loss following epileptiform activity. Epileptiform injury in hippocampal slice cultures was induced by 48 h exposure to 100 µM bicuculline methochloride (BMC). During the 24h recovery period following BMC treatment, lesion spread was observed in the CA1. A Cx43 mimetic peptide, applied during either the BMC treatment or recovery periods, produced concentration- and exposure time-dependent neuroprotection, as measured by propidium iodide uptake at the end of the recovery period. During the BMC period, peptide concentrations between 5 and 50 µM (sufficient to block hemichannels) had a protective effect while a substantial gap junction blockade with 500 µM peptide exacerbated the lesion. By contrast, all doses applied during the recovery period protected the CA1 region from further damage. The results indicate that while the slices are undergoing excessive neuronal firing and epileptic stress, gap junction communication appears to be essential for tissue survival but hemichannel opening may be damaging. Following epileptiform insult, however, gap junction communication plays a crucial role in the spread of neuronal damage. The findings from this study identify gap junction communication as a potential therapeutic target for epilepsy.