Repeatability of measuring corneal subbasal nerve fiber length in individuals with Type 2 Diabetes

Purpose: To analyze the repeatability of measuring nerve fiber length (NFL) from images of the human corneal subbasal nerve plexus using semiautomated software. Methods: Images were captured from the corneas of 50 subjects with type 2 diabetes mellitus who showed varying severity of neuropathy, using the Heidelberg Retina Tomograph 3 with Rostock Corneal Module. Semiautomated nerve analysis software was independently used by two observers to determine NFL from images of the subbasal nerve plexus. This procedure was undertaken on two occasions, 3 days apart. Results: The intraclass correlation coefficient values were 0.95 (95% confidence intervals: 0.92–0.97) for individual subjects and 0.95 (95% confidence intervals: 0.74–1.00) for observer. Bland-Altman plots of the NFL values indicated a reduced spread of data with lower NFL values. The overall spread of data was less for (a) the observer who was more experienced at analyzing nerve fiber images and (b) the second measurement occasion. Conclusions: Semiautomated measurement of NFL in the subbasal nerve fiber layer is highly repeatable. Repeatability can be enhanced by using more experienced observers. It may be possible to markedly improve repeatability when measuring this anatomic structure using fully automated image analysis software.

Increased Langerhan cell density and corneal nerve damage in diabetic patients : role of immune mechanisms in human diabetic neuropathy

Aim/hypothesis Immune mechanisms have been proposed to play a role in the development of diabetic neuropathy. We employed in vivo corneal confocal microscopy (CCM) to quantify the presence and density of Langerhans cells (LCs) in relation to the extent of corneal nerve damage in Bowman's layer of the cornea in diabetic patients. Methods 128 diabetic patients aged 58±1 yrs with a differing severity of neuropathy based on Neuropathy Deficit Score (NDS—4.7±0.28) and 26 control subjects aged 53±3 yrs were examined. Subjects underwent a full neurological evaluation, evaluation of corneal sensation with non-contact corneal aesthesiometry (NCCA) and corneal nerve morphology using corneal confocal microscopy (CCM). Results The proportion of individuals with LCs was significantly increased in diabetic patients (73.8%) compared to control subjects (46.1%), P=0.001. Furthermore, LC density (no/mm2) was significantly increased in diabetic patients (17.73±1.45) compared to control subjects (6.94±1.58), P=0.001 and there was a significant correlation with age (r=0.162, P=0.047) and severity of neuropathy (r=−0.202, P=0.02). There was a progressive decrease in corneal sensation with increasing severity of neuropathy assessed using NDS in the diabetic patients (r=0.414, P=0.000). Corneal nerve fibre density (P<0.001), branch density (P<0.001) and length (P<0.001) were significantly decreased whilst tortuosity (P<0.01) was increased in diabetic patients with increasing severity of diabetic neuropathy. Conclusion Utilising in vivo corneal confocal microscopy we have demonstrated increased LCs in diabetic patients particularly in the earlier phases of corneal nerve damage suggestive of an immune mediated contribution to corneal nerve damage in diabetes.

Corneal confocal microscopy : a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

OBJECTIVE: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. ---------- RESEARCH DESIGN AND METHODS: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). ---------- RESULTS: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = −0.475, P < 0.0001; NBD r = −0.511, P < 0.0001; and NFL r = −0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm2 with a sensitivity of 0.82 (95% CI 0.68–0.92) and specificity of 0.52 (0.40–0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm2 with a sensitivity of 0.71 (0.42–0.92) and specificity of 0.64 (0.54–0.74). ---------- CONCLUSIONS: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. Established diabetic neuropathy leads to pain and foot ulceration. Detecting neuropathy early may allow intervention with treatments to slow or reverse this condition (1). Recent studies suggested that small unmyelinated C-fibers are damaged early in diabetic neuropathy (2–4) but can only be detected using invasive procedures such as sural nerve biopsy (4,5) or skin-punch biopsy (6–8). Our studies have shown that corneal confocal microscopy (CCM) can identify early small nerve fiber damage and accurately quantify the severity of diabetic neuropathy (9–11). We have also shown that CCM relates to intraepidermal nerve fiber loss (12) and a reduction in corneal sensitivity (13) and detects early nerve fiber regeneration after pancreas transplantation (14). Recently we have also shown that CCM detects nerve fiber damage in patients with Fabry disease (15) and idiopathic small fiber neuropathy (16) when results of electrophysiology tests and quantitative sensory testing (QST) are normal. In this study we assessed corneal sensitivity and corneal nerve morphology using CCM in diabetic patients stratified for the severity of diabetic neuropathy using neurological evaluation, electrophysiology tests, and QST. This enabled us to compare CCM and corneal esthesiometry with established tests of diabetic neuropathy and define their sensitivity and specificity to detect diabetic patients with early neuropathy and those at risk of foot ulceration.

Professor Emeritus Leo G Carney Optometry's quiet achiever

Perhaps more than any other sub-discipline in optometry and vision science, the academic field of cornea and contact lenses is populated by an assortment of extroverted and flamboyant characters who constantly travel the world, entertaining clinicians with dazzling audiovisual presentations, informing them about the latest advances in the field and generally promoting their own scientific agendas. The antithesis of this is Leo Carney (Figure 1), a highly accomplished researcher, teacher, mentor and administrator, who has quietly and with great dignity carved out an impressive career in academic optometry. Indeed, Leo Carney is optometry's quintessential ‘quiet achiever’

Obituary - Rigid contact lenses

Scleral and corneal rigid lenses represented 100 per cent of the contact lens market immediately prior to the invention of soft lenses in the mid-1960s. In the United Kingdom today, rigid lenses comprise 2 per cent of all new lens fits. Low rates of rigid lens fitting are also apparent in 27 other countries which have recently been surveyed. Thus, the 1998 prediction of the author that rigid lenses – also referred to as ‘rigid gas permeable’ (RGP) lenses or ‘gas permeable’ (GP) lenses – would be obsolete by the year 2010 has essentially turned out to be correct. In this obituary, the author offers 10 reasons for the demise of rigid lens fitting: initial rigid lens discomfort; intractable rigid lens-induced corneal and lid pathology; extensive soft lens advertising; superior soft lens fitting logistics; lack of rigid lens training opportunities; redundancy of the rigid lens ‘problem solver’ function; improved soft toric and bifocal/varifocal lenses; limited uptake of orthokeratology; lack of investment in rigid lenses; and the emergence of aberration control soft lenses. Rigid lenses are now being fitted by a minority of practitioners with specialist skills/training. Certainly, rigid lenses can no longer be considered as a mainstream form of contact lens correction. May their dear souls (bulk properties) rest in peace.

How optometrists record corneal staining

Purpose: The aim of this study was to determine current approaches adopted by optometrists to the recording of corneal staining following fluorescein instillation. Methods: An anonymous ‘record-keeping task’ was sent to all 756 practitioners who are members of the Queensland Division of Optometrists Association Australia. This task comprised a form on which appeared a colour photograph depicting contact lens solution-induced corneal staining. Next to the photograph was an empty box, in which practitioners were asked to record their observations. Practitioners were also asked to indicate the level of severity of the condition at which treatment would be instigated. Results: Completed task forms were returned by 228 optometrists, representing a 30 per cent response rate. Ninety-two per cent of respondents offered a diagnosis. The most commonly used descriptive terms were ‘superficial punctate keratitis’ (36 per cent of respondents) and ‘punctate staining’ (29 per cent). The level of severity and location of corneal staining were noted by 69 and 68 per cent of respondents, respectively. A numerical grade was assigned by 44 per cent of respondents. Only three per cent nominated the grading scale used. The standard deviation of assigned grades was � 0.6. The condition was sketched by 35 per cent of respondents and two per cent stated that they would take a photograph of the eye. Ten per cent noted the eye in which the condition was being observed. Opinions of the level of severity at which treatment for corneal staining should be instigated varied considerably between practitioners, ranging from ‘any sign of corneal staining’ to ‘grade 4 staining’. Conclusion: Although most practitioners made a sensible note of the condition and properly recorded the location of corneal staining, serious deficiencies were evident regarding other aspects of record-keeping. Ongoing programs of professional optometric education should reinforce good practice in relation to clinical record-keeping.

An international survey of contact lens prescribing for presbyopia

Purpose: The aim was to determine world-wide patterns of fitting contact lenses for the correction of presbyopia. Methods: Up to 1,000 survey forms were sent to contact lens fitters in each of 38 countries between January and March every year over five consecutive years (2005 to 2009). Practitioners were asked to record data relating to the first 10 contact lens fittings or refittings performed after receiving the survey form. Results: Data were received relating to 16,680 presbyopic (age 45 years or older) and 84,202 pre-presbyopic (15 to 44 years) contact lens wearers. Females are over-represented in presbyopic versus pre-presbyopic groups, possibly reflecting a stronger desire for the cosmetic benefits of contact lenses among older women. The extent to which multifocal and monovision lenses are prescribed for presbyopes varies considerably among nations, ranging from 79 per cent of all soft lenses in Portugal to zero in Singapore. There appears to be significant under-prescribing of contact lenses for the correction of presbyopia, although for those who do receive such corrections, three times more multifocal lenses are fitted compared with monovision fittings. Presbyopic corrections are most frequently prescribed for full-time wear and monthly replacement. Conclusions: Despite apparent improvements in multifocal design and an increase in available multifocal options in recent years, practitioners are still under-prescribing with respect to the provision of appropriate contact lenses for the correction of presbyopia. Training of contact lens practitioners in presbyopic contact lens fitting should be accelerated and clinical and laboratory research in this field should be intensified to enhance the prospects of meeting the needs of presbyopic contact lens wearers more fully.

Corneal sensitivity as an ophthalmic marker of diabetic neuropathy

Purpose. The objective of this study was to explore the discriminative capacity of non-contact corneal esthesiometry (NCCE) when compared with the neuropathy disability score (NDS) score—a validated, standard method of diagnosing clinically significant diabetic neuropathy. Methods. Eighty-one participants with type 2 diabetes, no history of ocular disease, trauma, or surgery and no history of systemic disease that may affect the cornea were enrolled. Participants were ineligible if there was history of neuropathy due to non-diabetic cause or current diabetic foot ulcer or infection. Corneal sensitivity threshold was measured on the eye of dominant hand side at a distance of 10 mm from the center of the cornea using a stimulus duration of 0.9 s. The NDS was measured producing a score ranging from 0 to 10. To determine the optimal cutoff point of corneal sensitivity that identified the presence of neuropathy (diagnosed by NDS), the Youden index and “closest-to-(0,1)” criteria were used. Results. The receiver-operator characteristic curve for NCCE for the presence of neuropathy (NDS ≥3) had an area under the curve of 0.73 (p = 0.001) and, for the presence of moderate neuropathy (NDS ≥6), area of 0.71 (p = 0.003). By using the Youden index, for an NDS ≥3, the sensitivity of NCCE was 70% and specificity was 75%, and a corneal sensitivity threshold of 0.66 mbar or higher indicated the presence of neuropathy. When NDS ≥6 (indicating risk of foot ulceration) was applied, the sensitivity was 52% with a specificity of 85%. Conclusions. NCCE is a sensitive test for the diagnosis of minimal and more advanced diabetic neuropathy and may serve as a useful surrogate marker for diabetic and perhaps other neuropathies.

Long term immunity to live attenuated Japanese encephalitis chimeric virus vaccine : randomized, double-blind, 5-year phase II study in healthy adults.

In a randomized, double-blind study, 202 healthy adults were randomized to receive a live, attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) and placebo 28 days apart in a cross-over design. A subgroup of 98 volunteers received a JE-CV booster at month 6. Safety, immunogenicity, and persistence of antibodies to month 60 were evaluated. There were no unexpected adverse events (AEs) and the incidence of AEs between JE-CV and placebo were similar. There were three serious adverse events (SAE) and no deaths. A moderately severe case of acute viral illness commencing 39 days after placebo administration was the only SAE considered possibly related to immunization. 99% of vaccine recipients achieved a seroprotective antibody titer ≥ 10 to JE-CV 28 days following the single dose of JE-CV, and 97% were seroprotected at month 6. Kaplan Meier analysis showed that after a single dose of JE-CV, 87% of the participants who were seroprotected at month 6 were still protected at month 60. This rate was 96% among those who received a booster immunization at month 6. 95% of subjects developed a neutralizing titer ≥ 10 against at least three of the four strains of a panel of wild-type Japanese encephalitis virus (JEV) strains on day 28 after immunization. At month 60, that proportion was 65% for participants who received a single dose of JE-CV and 75% for the booster group. These results suggest that JE-CV is safe, well tolerated and that a single dose provides long-lasting immunity to wild-type strains

Bushfire sustainability : Strategies for reconciling bushfire and biodiversity with daily life

This exhibition and catalogue provides a visual record of student work exhibited at the Australian Institute of Architects offices in Brisbane from November 15 to 29, 2010. The exhibition features the final design outcomes of the inaugural Bushfire Sustainability unit conducted at QUT in semester two, 2010. The core objective of this unit was to develop our students’ skills in collaborative practice in design, research and presentation. The theme of ‘bushfire sustainability’ was chosen because living sustainably in bushfire prone landscapes presents a number of problems, the nature of which might only be resolved via multidisciplinary collaboration among the design disciplines. The students involved represent the disciplines of Interior Design, Landscape Architecture, Industrial Design, Architecture and Sustainability – all from within the School of Design at QUT. 55 students, mostly in their third year of study, worked in teams of five (one from each discipline) to design one of a number of homes in highly bushfire prone sites in either Western Australia or SE Queensland. This year level and the interdisciplinary mix are perhaps the best placed to resolve these problems: being unrestrained from the burdens of professional practice and technical overload they retain the potential for innovative, lateral thinking across the range of spatial scales and philosophical perspectives associated with inhabitation of bushfire prone landscapes. It is envisaged that, through the ‘vehicle’ of this design research, that the students’ work will contribute to understandings of how creative design disciplines might respond to this significant national problem, which hitherto has been attended to primarily by engineering and the sciences.

Mental harm, rescuers and the Civil Liability Act 2002 (NSW)

At common law, a duty of care may be owed to a claimant who suffers nervous shock or pure mental harm due to witnessing, or hearing about, physical injury caused to another due to a defendant’s negligence. “Pure mental harm” is the ‘impairment of a person’s mental condition’ that is not suffered as a consequence of any other kind of personal injury to them. However, as many accidents have the potential to create a wide circle of mental suffering to bystanders, family members or others not physically injured themselves, it has traditionally been ‘thought impolitic that everybody so affected should be able to recover damages from the tortfeasor.’ ‘To allow such extended recovery would stretch liability too far.’ Nevertheless, whilst adopting a restrictive approach to liability, the common law courts have recognised that a defendant might owe a duty in relation to the pure mental harm suffered by one who foreseeably attends an accident scene to rescue another from a situation created by the defendant’s negligence.

Vulnerability, insurance and policy: The learner driver's standard of care

In Cook v Cook the Australian High Court held that the standard of reasonable care owed by a learner driver to an instructor, conscious of the driver’s lack of experience, was lower than that owed to other passengers and road users. Recently, in Imbree v McNeilly, the High Court declined to follow this principle, concluding that the driver’s status or relationship with the claimant should no longer influence or alter the standard of care owed. The decision therefore provides an opportunity to re-examine the rationale and policy behind current jurisprudence governing the standard of care owed by learner drivers. In doing so, this article considers the principles relevant to determining the standard and Imbree’s implications for other areas of tort law and claimant v defendant relationships. It argues that Imbree was influenced by changing judicial perceptions concerning the vulnerability of driving instructors and the relevance of insurance to tortious liability.

Causing economic harm to property developers : damages for starting an incurably bad appeal?

A recent decision of the Queensland Court of Appeal involved an unusual statement of claim made on behalf of the developer of a proposed resort in Port Douglas. The decision is The Beach Club Port Douglas Pty Ltd v Page [2005] QCA 475. The issue The defendant had objected to a development application of the plaintiff developer and lodged an appeal in the Planning and Environment Court against the council decision granting a development permit. The main issue in the Planning and Environment Court was whether the site coverage of the proposed resort was excessive. In a separate action (the subject matter of the present appeal), the plaintiff developer claimed damages for ‘negligence’ alleging that the defendant had breached a duty of care not to appeal without properly or reasonably assessing whether the development qualified for a permit given that the resort qualified for the maximum allowable site coverage. It was alleged that the appeal lodged by the defendant in the Planning and Environment Court had no reasonable prospects of success and that any reasonable person properly advised would know, or ought reasonably to have known, that to be so. The defendant had been “put on notice” that the plaintiff would incur loss of $10,000 for every day there was a delay in starting construction of the resort. The claim made by the developer required the court to consider those circumstances where a person may lawfully and deliberately cause economic harm to another. Was a duty of care owed by the defendant for negligent conduct of litigation that caused economic loss to the plaintiff?

Ending the life of the act/omission dispute: Causation in withholding and withdrawing life-sustaining measures

My aim in this paper is to challenge the increasingly common view in the literature that the law on end of life decision making is in disarray and is in need of urgent reform. My argument is that this assessment of the law is based on assumptions about the relationship between the identity of the defendant and their conduct, and about the nature of causation, which, on examination, prove to be indefensible. I then provide a clarification of the relationship between causation and omissions which proves that the current legal position does not need modification, at least on the grounds that are commonly advanced for the converse view. This enables me, in conclusion, to clarify important conceptual and moral differences between withholding, refusing and withdrawing life-sustaining measures on the one hand, and assisted suicide and euthanasia, on the other.