Safe eye surgery: non-technical aspects

The traditional training of surgeons focused exclusively on developing knowledge, clinical expertise, and technical (surgical) skills. However, analyses of the reasons for adverse events in surgery have revealed that many underlying causes originate from behavioural or non-technical aspects of performance (eg, poor communication among members of the surgical team) rather than from a lack of surgical (ie, technical) skills. Therefore, technical skills appear to be necessary but not sufficient to ensure patient safety. Paying attention to non-technical skills, such as team working, leadership, situation awareness, decision making, and communication, will increase the likelihood of maintaining high levels of error-free performance. Identification and training of non-technical skills has been developed for high-risk careers, such as civil aviation and nuclear power. Only recently, training in non-technical skills has been adopted by the surgical world and anaesthetists. Non-technical skills need to be tailored to the environment where they are used, and eye surgery has some substantial differences compared with other surgical areas, for example, high volume of surgery, use of local anaesthetics, and very sophisticated equipment. This review highlights the need for identification of the non-technical skills relevant to eye surgeons and promotion of their use in the training of eye surgeons.

Polyamine system in developing rat eye and an animal model of retinopathy of prematurity

BACKGROUND: In experimental models of retinopathy of prematurity (ROP), a vasoproliferative disorder of the retina, retinal lesions are usually assessed by morphological examination. However, studies suggest that the polyamine system may be useful in monitoring proliferation processes. For this reason, polyamine concentrations in rat erythrocytes (RBC) and the regulation of polyamine system in rat eyes under the conditions relevant to ROP were investigated. METHODS: Newborn Wistar rats were reared in room air (control) or exposed first to hyperoxia (60% or 80% oxygen, 2 weeks) and then to normoxia (relative hypoxia, 1 or 2 weeks). Blood was collected from orbital vessels at 2 weeks of age and before death. Polyamine system-related enzyme activities were measured in retina and lens with radioassays. Polyamines were quantified by fluorometry after extraction, dansylation and HPLC separation. RESULTS: Oxygen (80% only) significantly decreased RBC polyamine concentrations, which then markedly increased after rats were transferred for a week to normal air, suggesting retardation of growth processes and compensatory stimulation, respectively. However, polyamine system changes in the rat eye were not so pronounced. Enzyme activities and polyamine concentrations tended to be lower in retina after hyperoxia and were only slightly higher, with the exception of ornithine decarboxylase, after a subsequent 1 week of normoxia. In litters subjected to normoxia for longer periods no changes were found. CONCLUSION: The transient and short-lived alteration in polyamine metabolism, especially in the eye, suggests that exposure of newborn rats to high oxygen supplementation followed by normoxia does not necessarily result in marked retinopathy.

Focal irradiation of perforating eye injuries

Plaques constructed with 125I were used to irradiate the sites of perforating ocular injuries in rabbits. An approximate dose of 16Gy given over a period of 6 days was shown to significantly reduce intraocular cellular proliferation when irradiation was commenced within 24 hours after injury. If irradiation was delayed until day 5, this reduction in cellular proliferation and intraocular membrane formation did not occur. Smaller radiation doses of approximately 6Gy given within 24 hours post-injury and administered over 6 days also reduced the extent of cellular proliferation but was not as effective as the 16Gy dose.

Evaluation of Microcollimated Pars Plana External Beam Radiation in the Porcine Eye

Purpose: To evaluate the clinical and histological side effects of a prototype stereotactic radiotherapy system delivering microcollimated external beam radiation through pars plana in porcine eyes.

Methods: Five Yucatan mini-swine (10 eyes) were randomized to five treatment groups. Eight eyes were dosed with X-ray radiation on Day 1, and two eyes served as untreated controls. Treated eyes received doses up to 60 Gy to the retina and up to 130 Gy to the sclera using single or overlapping beams. The treatment beams were highly collimated such that the diameter was approximately 2.5 mm on the sclera and 3 mm on the retinal surface. Fundus photography, fluorescein angiography (FA), and spectral domain optical coherence tomography (SD-OCT) were obtained on days 7, 30, 60, and 110. Images were examined by a masked grader and evaluated for abnormalities. Animals were sacrificed on day 111 and gross and histopathological analysis was conducted.

Results: Histological and gross changes to eye structures including conjunctiva and lens were minimal at all doses. Fundus, FA, and SD-OCT of the targeted region failed to disclose any abnormality in the control or 21 Gy treated animals. In the 42 and 60 Gy animals, hypopigmented spots were noted after treatment on clinical exam, and corresponding hyperfluorescent staining was seen in late frames. No evidence of choroidal hypoperfusion was seen. The histological specimens from the 60 Gy animals showed photoreceptor loss and displacement of cone nuclei.

Conclusion: Transcleral stereotactic radiation dosing in porcine eyes can be accomplished with no significant adverse events as doses less than 42 Gy.

Newly Acquired Fear of Falling Leads to Altered Eye Movement Patterns and Reduced Stepping Safety: A Case Study

This opportune case study describes visual and stepping behaviours of an 87 year old female (P8), both prior to, and following two falls. Before falling, when asked to walk along a path containing two stepping guides positioned before and after an obstacle, P8 generally visually fixated the first stepping guide until after foot contact inside it. However, after falling P8 consistently looked away from the stepping guide before completing the step into it in order to fixate the upcoming obstacle in her path. The timing of gaze redirection away from the target (in relation to foot contact inside it) correlated with absolute stepping error. No differences in eyesight, cognitive function, or balance were found between pre- and post-fall recordings. However, P8 did report large increases in fall-related anxiety and reduced balance confidence, supporting previously suggested links between anxiety/increased fear or falling and maladaptive visual/stepping behaviours. The results represent a novel insight into how psychological and related behavioural factors can change in older adults following a fall, and provide a possible partial rationalisation for why recent fallers are more likely to fall again in the following 12 months. These findings highlight novel possibilities for falls prevention and rehabilitation.

Will VEGF Trap-Eye reduce the treatment burden in neovascular age-related macular degeneration?

Evaluation of: Brown DM, Heier JS, Ciulla T et al. Primary end point results of a Phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration. Ophthalmology 118(6), 1089-1097 (2011); Heier JS, Boyer D, Nguyen QD et al. The 1-year results of CLEAR-IT 2, a Phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing. Ophthalmology 118(6), 1098-1106 (2011). Age-related macular degeneration is the most common cause of blindness in older adults in western countries, and is likely to become the largest cause of irreversible sight loss in the developing world. Treatments such as ranibizumab and bevacizumab that inhibit VEGF have improved visual outcomes markedly. Controlled trials and clinical experience have shown that the best outcomes are achieved when monthly treatment has been administered over 2 years. This poses a significant burden on health providers and patients. A novel inhibitor of VEGF, VEGF Trap-Eye, which allows less frequent dosing without loss of efficacy, has emerged as a potential treatment. CLEAR-IT 2 was a prospective randomized Phase II trial designed to assess the safety, tolerability and the anatomic and visual effects of repeated treatments with a range of doses of VEGF Trap-Eye. Impressive anatomic and visual improvements were noted with no safety concerns. © 2011 Expert Reviews Ltd.

Clinical Characteristics of Reticular Pseudodrusen in the Fellow Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration

Purpose: To describe associations between reticular pseudodrusen, individual characteristics, and retinal function.

Design: Cohort study.

Participants: We recruited 105 patients (age range, 52–93 years) who had advanced neovascular age-related macular degeneration (AMD) in only 1 eye from 3 clinical centers in Europe.

Methods: Minimum follow-up was 12 months. The eye selected for study was the fellow eye without advanced disease. Clinical measures of vision were distance visual acuity, near visual acuity, and results of the Smith-Kettlewell low-luminance acuity test (SKILL). Fundus imaging included color photography, red-free imaging, blue autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and optical coherence tomography using standardized protocols. These were used to detect progression to neovascular AMD in the study eye during follow-up. All imaging outputs were graded for the presence or absence of reticular pseudodrusen (RPD) using a multimodal approach. Choroidal thickness was measured at the foveal center and at 2 other equidistant locations from the fovea (1500 μm) nasally and temporally. Metrics on retinal thickness and volume were obtained from the manufacturer-supplied automated segmentation readouts.

Main Outcome Measures: Presence of RPD, distance visual acuity, near visual acuity, SKILL score, choroidal thickness, retinal thickness, and retinal volume.

Results: Reticular pseudodrusen was found in 43 participants (41%) on 1 or more imaging method. The SKILL score was significantly worse in those with reticular drusen (mean score ± standard deviation [SD, 38±12) versus those without (mean score ± SD, 33±9) (P = 0.034). Parafoveal retinal thickness, parafoveal retinal volume, and all of the choroidal thickness parameters measured were significantly lower in those with reticular drusen than in those without. The presence of RPD was associated with development of neovascular AMD when corrected for age and sex (odds ratio, 5.5; 95% confidence interval, 1.1–28.8; P = 0.042). All participants in whom geographic atrophy developed during follow-up had visible RPD at baseline.

Conclusions: Significant differences in retinal and choroidal anatomic features, visual function, and risk factor profile exist in unilateral neovascular AMD patients with RPD compared with those without; therefore, such patients should be monitored carefully because of the risk of developing bilateral disease.

Retinal Vascular Caliber, Iris Color, and Age-Related Macular Degeneration in the Irish Nun Eye Study

Pupose. To evaluate the relationship between retinal vascular caliber (RVC), iris color and age-related macular degeneration (AMD) in elderly Irish nuns. Methods. Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study were assessed from digital photographs with a standardized protocol using computer-assisted software. Macular images were graded according to the modified Wisconsin age-related maculopathy grading system. Regression models were used to assess associations, adjusting for age, mean arterial blood pressure, body mass index, refraction and fellow RVC. Results. In total, 1122 (91%) participants had gradable retinal images of sufficient quality for vessel assessment (mean age: 76.3 years [range: 56-100 years]). In an unadjusted analysis, we found some support for a previous finding that individuals with blue iris color had narrower retinal venules compared to those with brown iris color (P<0.05) but this was no longer significant after adjustment. AMD status was categorized as no AMD, any AMD and late AMD only. Individuals with any AMD (early or late AMD) had significantly narrower arterioles and venules compared to those with no AMD in an unadjusted analysis but this was no longer significant after adjustment. A non-significant reduced risk of any AMD or late AMD only was observed in association with brown compared to blue iris color, in both unadjusted and adjusted analyses. Conclusions. RVC was not significantly associated with iris color or early/late AMD after adjustment for confounders. A lower but non-significant AMD risk was observed in those with brown compared to blue iris color.

Identification and Functional Analysis of a Novel Tryptophyllin Peptide from the Skin of the Red-eye Leaf Frog, Agalychnis callidryas

Amphibian skin has proved repeatedly to be a largely untapped source of bioactive peptides and this is especially true of members of the Phyllomedusinae subfamily of frogs native to South and Central America. Tryptophyllins are a group of peptides mainly found in the skin of members of this genus. In this study, a novel tryptophyllin (TPH) type 3 peptide, named AcT-3, has been isolated and structurally-characterised from the skin secretion and lyophilised skin extract of the red-eye leaf frog, Agalychnis callidryas. The peptide was identified in and purified from the skin secretion by reverse-phase HPLC. MALDI-TOF mass spectrometry and MS/MS fragmentation sequencing established its primary structure as: pGlu-Gly-Lys-Pro-Tyr-Trp-Pro-Pro-Pro-Phe-Leu-Pro-Glu, with a non-protonated molecular mass of 1538.19Da. The mature peptide possessed the canonical N-terminal pGlu residue that arises from post-translational modification of a Gln residue. The deduced open-reading frame consisted of 63 amino acid residues encoding a highly-conserved signal peptide of approximately 22 amino acid residues, an intervening acidic spacer peptide domain, a single AcT-3 encoding domain and a C terminal processing site. A synthetic replicate of AcT-3 was found to antagonise the effect of BK on rat tail artery smooth muscle and to contract the intestinal smooth muscle preparations. It was also found that AcT-3 could dose-dependently inhibit the proliferation of human prostate cancer cell lines after 72h incubation.