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Nathan Efron - Top 30 Publications

Ophthalmic and clinical factors that predict four-year development and worsening of diabetic retinopathy in type 1 diabetes.

To investigate the role of ophthalmic imaging markers - namely retinal thickness measures and corneal nerve morphology - in predicting four-year development and worsening of diabetic retinopathy (DR) in type 1 diabetes (T1DM).

Contact lenses continue to evolve.

Rethinking contact lens aftercare.

The evolution of contact lens technology and clinical practice over the past three decades has been remarkable, with dramatic improvements in material biocompatibility, better lens designs and care systems, and more flexible and convenient modalities of wear. However, our approach to the aftercare examination has remained conservative, with the general modus operandi having not fully evolved from the difficult, early years of fitting non-regular replacement rigid and low water content hydrogel lenses. In this paper, we review current aftercare practice and in particular, the preferred frequency that lens wearers should return for routine visits and the appropriateness of regulations governing contact lens prescription expiry. Four key clinical reasons for conducting a routine aftercare visit are identified: preserving ocular health, maintaining good vision, optimising comfort and ensuring satisfactory lens fitting performance. Commercial reasons for conducting aftercare visits are also considered. A decision matrix is presented to help practitioners decide on an appropriate time interval between routine aftercare visits. The first aftercare visit should always take place within one to two weeks of lens dispensing. After this, the following time intervals between routine aftercare visits are advised as a general guideline: soft daily disposable, 24 months; soft daily reusable and rigid daily wear, 12 months; soft and rigid extended wear, six months. These aftercare visit frequencies may need to be adjusted when rapid rates of refractive change are anticipated, such as every six months during child/teenager myopic progression and every 12 months during the advancement of presbyopia. Numerous clinical caveats for varying these recommended aftercare frequencies are also discussed. Those new to lens wear should be seen within the first two months of lens dispensing. Regulatory authorities charged with the responsibility of stipulating the validity of a contact lens prescription should continue to allow optometrists to set an expiry date relevant to the circumstances of individual lens wearers.

Presence of Peripheral Neuropathy Is Associated With Progressive Thinning of Retinal Nerve Fiber Layer in Type 1 Diabetes.

Reduced retinal nerve fiber layer (RNFL) thickness has been demonstrated in patients with diabetic peripheral neuropathy (DPN) in cross-sectional studies. This prospective study defines longitudinal alterations to the RNFL thickness in individuals with type 1 diabetes without (DPN-ve) and with (DPN+ve) DPN and in relation to risk factors for nerve damage.

TFOS DEWS II iatrogenic report.

Dry eye can be caused by a variety of iatrogenic interventions. The increasing number of patients looking for eye care or cosmetic procedures involving the eyes, together with a better understanding of the pathophysiological mechanisms of dry eye disease (DED), have led to the need for a specific report about iatrogenic dry eye within the TFOS DEWS II. Topical medications can cause DED due to their allergic, toxic and immuno-inflammatory effects on the ocular surface. Preservatives, such as benzalkonium chloride, may further aggravate DED. A variety of systemic drugs can also induce DED secondary to multiple mechanisms. Moreover, the use of contact lens induces or is associated with DED. However, one of the most emblematic situations is DED caused by surgical procedures such as corneal refractive surgery as in laser-assisted in situ keratomileusis (LASIK) and keratoplasty due to mechanisms intrinsic to the procedure (i.e. corneal nerve cutting) or even by the use of postoperative topical drugs. Cataract surgery, lid surgeries, botulinum toxin application and cosmetic procedures are also considered risk factors to iatrogenic DED, which can cause patient dissatisfaction, visual disturbance and poor surgical outcomes. This report also presents future directions to address iatrogenic DED, including the need for more in-depth epidemiological studies about the risk factors, development of less toxic medications and preservatives, as well as new techniques for less invasive eye surgeries. Novel research into detection of early dry eye prior to surgeries, efforts to establish appropriate therapeutics and a greater attempt to regulate and oversee medications, preservatives and procedures should be considered.

Corneal Confocal Microscopy Is Emerging as a Powerful Diagnostic Tool for Assessing Systemic Neurologic Disease.

Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy.

Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible technique that quantifies small nerve fibres. We have compared the diagnostic capability of CCM against a range of established measures of nerve damage in patients with diabetic neuropathy.

Optical coherence tomography predicts 4-year incident diabetic neuropathy.

To examine the capability of optical coherence tomography-derived retinal thickness measures in detecting 4-year incident diabetic peripheral neuropathy (DPN).

Corneal confocal microscopy best identifies the development and progression of neuropathy in patients with type 1 diabetes.

A sub-set of 38 individuals with type 1 diabetes that fulfilled a strict criterion of "normal" classification for all 7 measures of neuropathy at baseline, were identified and followed. Corneal nerve morphology, as captured with corneal confocal microscopy demonstrated the greatest, and most sustained degeneration over a 4 year period.

Small-fibre neuropathy in men with type 1 diabetes and erectile dysfunction: a cross-sectional study.

The aim of this study was to identify the contribution of small- and large-fibre neuropathy to erectile dysfunction in men with type 1 diabetes mellitus.

Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy.

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine.

Contact lens wear is intrinsically inflammatory.

Eye-care practitioners typically associate ocular inflammation during contact lens wear with serious complications such as microbial keratitis; however, more subtle mechanisms may be at play. This paper tests the notion that contact lens wear is intrinsically inflammatory by exploring whether uncomplicated contact lens wear meets the classical, clinical definition of inflammation - rubor (redness), calor (heat), tumor (swelling), dolor (pain) and functio laesa (loss of function) - as well as the contemporary, sub-clinical definition of inflammation (cellular and biochemical reactions). It is demonstrated that all of these clinical and sub-clinical criteria are met with hydrogel lens wear and most are met with silicone hydrogel lens wear, indicating that uncomplicated contact lens wear is intrinsically inflammatory. Consideration of both traditional and contemporary thinking about the role of inflammation in the human body leads to the perhaps surprising conclusion that the chronic, low grade, sub-clinical inflammatory status of the anterior eye during contact lens wear, which may be termed 'para-inflammation', is a positive, protective phenomenon, whereby up-regulation of the immune system, in a non-damaging way, maintains the eye in a state of 'heightened alert', ready to ward off any extrinsic noxious challenge. Characterisation of this inflammatory status may lead to the development of lens engineering or pharmacological strategies to modulate contact lens-induced inflammation, so as to render lens wear more safe and comfortable.

Focal loss volume of ganglion cell complex in diabetic neuropathy.

The aim was to investigate the relationship between diabetic peripheral neuropathy (DPN) and abnormalities in ganglion cell complex (GCC); specifically, focal loss volume (FLV) and global loss volume (GLV).

A sixteen year survey of Canadian contact lens prescribing.

To understand long-term contact lens prescribing habits of Canadian optometrists.

Abnormal Anterior Corneal Morphology in Diabetes Observed Using In Vivo Laser-scanning Confocal Microscopy.

To assess if diabetes alters corneal epithelial, anterior stromal and subbasal nerve plexus morphology and to determine the associations between these and other clinical variables.

A rapid decline in corneal small fibers and occurrence of foot ulceration and Charcot foot.

We present clinical, neuropathy and corneal nerve morphology data in a participant with type 2 diabetes who developed diabetic foot ulceration, partial amputation and Charcot during a longitudinal observational study. While conventional measures of neuropathy did not deteriorate significantly, corneal nerve parameters showed a rapid reduction prior to the development of foot complications.

Diagnostic capability of retinal thickness measures in diabetic peripheral neuropathy.

To examine the diagnostic capability of the full retinal and inner retinal thickness measures in differentiating individuals with diabetic peripheral neuropathy (DPN) from those without neuropathy and non-diabetic controls.

Characterization of Goblet Cells in a Pterygium Biopsy Using Laser Scanning Confocal Microscopy and Immunohistochemistry.

To confirm that structures presumed to be GCs observed using laser scanning confocal microscopy (LSCM) are actually GCs.

Longitudinal changes in Langerhans cell density of the cornea and conjunctiva in contact lens-induced dry eye.

The aim was to determine longitudinal changes in Langerhans cell density (LCD) in the human cornea and conjunctiva during asymptomatic and symptomatic contact lens wear.

Repeatability of Measuring Corneal Nerve Migration Rate in Individuals With and Without Diabetes.

To assess the repeatability of measuring the corneal nerve migration rate in individuals with and without neuropathy.

Time Course of Changes in Goblet Cell Density in Symptomatic and Asymptomatic Contact Lens Wearers.

To investigate longitudinal changes in goblet cell density (GCD) in contact lens (CL) wearers who do and do not develop symptoms of dry eye (DE).

A Proposed New Measure of Corneal Sensitivity.

Lid wiper epitheliopathy.

Some recent research has resulted in a hypothesis that there is a common 'lid wiper' region that is apposite to the ocular surface or anterior lens surface (where contact lenses are worn), responsible for spreading tears during blinking. In the upper eyelid, it extends about 0.6 mm from the crest of the sharp posterior (inner) lid border (i.e. the mucocutaneous junction, or line of Marx) to the subtarsal fold superiorly and from the medial upper punctum to the lateral canthus horizontally. Histologically, it is seen as an epithelial elevation comprising of stratified epithelium with a transitional conjunctival structure of (moving posteriorly) squamous cells then cuboidal cells, with some parakeratinised cells and goblet cells. Lid wiper epitheliopathy (LWE) denotes staining of the lid wiper observed after instillation of dyes such as fluorescein, rose bengal or lissamine green. There have been some reports of higher rates of LWE in dry eye patients and contact lens wearers, but others have failed to find such associations. The primary cause of LWE is thought to be increased friction between the lid wiper and ocular or anterior contact lens surface due to inadequate lubrication, which could be caused by dry eye and may be exacerbated by factors such as abnormal blinking patterns, poor contact lens surface lubricity and adverse environmental influences. Recent evidence suggests that LWE is associated with sub-clinical inflammation. LWE has the potential to provide the missing mechanistic link between clinical observation and symptoms associated with dry eye and contact lens wear. Clinical and fundamental research into LWE is still in its infancy and in many instances equivocal; however, it is an idea that provides a potentially important new avenue for further investigation of anterior eye discomfort associated with ocular dryness and contact lens wear.

Inflammatory Cell Upregulation of the Lid Wiper in Contact Lens Dry Eye.

To determine if Langerhans cells in the lid wiper are upregulated in contact lens-induced dry eye (CLIDE).

Development of a Novel Technique to Measure Corneal Nerve Migration Rate.

We have developed a novel technique to measure in vivo corneal nerve migration.

Retinal Tissue Thickness is Reduced in Diabetic Peripheral Neuropathy.

To investigate the relationship between diabetic peripheral neuropathy (DPN) and retinal tissue thickness.

Changes in corneal Langerhans cell density during the first few hours of contact lens wear.

To determine the impact of contact lens wear on Langerhans cell density (LCD) in the central cornea over an 8h period.

Retinal tissue thickness in type 1 and type 2 diabetes.

The objective was to investigate full retinal and inner retinal thickness in individuals with type 1 and type 2 diabetes.

Assessment of conjunctival goblet cell density using laser scanning confocal microscopy versus impression cytology.

To determine the association between conjunctival goblet cell density (GCD) assessed using in vivo laser scanning confocal microscopy and conjunctival impression cytology in a healthy population.

Risk Factors Associated With Corneal Nerve Alteration in Type 1 Diabetes in the Absence of Neuropathy: A Longitudinal In Vivo Corneal Confocal Microscopy Study.

The aim of this study was to determine alterations to the corneal subbasal nerve plexus (SNP) over 4 years using in vivo corneal confocal microscopy in participants with type 1 diabetes and to identify significant risk factors associated with these alterations.