The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer.

Corneal changes following short-term miniscleral contact lens wear

Purpose To examine the influence of short-term miniscleral contact lens wear on corneal shape, thickness and anterior surface aberrations. Methods Scheimpflug imaging was captured before, immediately following and 3 hours after a short period (3 hours) of miniscleral contact lens wear for 10 young (mean 27 ± 5 years), healthy participants. Natural diurnal variations were considered by measuring baseline diurnal changes obtained on a separate control day without contact lens wear. Results Small but significant anterior corneal flattening was observed immediately following lens removal (overall mean 0.02 ± 0.03 mm, p < 0.001) which returned to baseline levels three hours after lens removal. During the three hour recovery period significant corneal thinning (-13.4 ± 10.5 μm) and posterior surface flattening (0.03 ± 0.02 mm) were also observed (both p < 0.01). The magnitude of posterior corneal flattening during recovery correlated with the amount of corneal thinning (r = 0.69, p = 0.03). Central corneal clearance (maximum tear reservoir depth) was not associated with corneal swelling following lens removal (r = -0.24, p > 0.05). An increase in lower-order corneal astigmatism Z(2,2) was also observed following lens wear (mean -0.144 ± 0.075 μm, p = 0.02). Conclusions Flattening of the anterior corneal surface was observed immediately following lens wear, while ‘rebound’ thinning and flattening of the posterior surface was evident following the recovery period. Modern miniscleral contact lenses that vault the cornea may slightly influence corneal shape and power but do not induce clinically significant corneal oedema during short-term wear.

The effects of metabolic work rate and ambient environment on physiological tolerance times while wearing explosive and chemical personal protective equipment

This study evaluated the physiological tolerance times when wearing explosive and chemical (>35kg) personal protective equipment (PPE) in simulated environmental extremes across a range of differing work intensities. Twelve healthy males undertook nine trials which involved walking on a treadmill at 2.5, 4 and 5.5 km.h-1 in the following environmental conditions, 21, 30 and 37 °C wet bulb globe temperature (WBGT). Participants exercised for 60 min or until volitional fatigue, core temperature reached 39 °C, or heart rate exceeded 90% of maximum. Tolerance time, core temperature, skin temperature, mean body temperature, heart rate and body mass loss were measured. Exercise time was reduced in the higher WBGT environments (WBGT370.05) and work intensities (5.5<4<2.5 km.h-1; P<0.001). The majority of trials (85/108; 78.7%) were terminated due to participant’s heart rate exceeding 90% of their maximum. A total of eight trials (7.4%) lasted the full duration. Only nine (8.3%) trials were terminated due to volitional fatigue and six (5.6%) due to core temperatures in excess of 39 °C. These results demonstrate that physiological tolerance times are influenced by the external environment and workload, and that cardiovascular strain is the limiting factor to work tolerance when wearing this heavy multi layered PPE.

Prevalence of malnutrition, obesity and nutritional risk of Australian paediatric inpatients: A national one-day snapshot

Aim Low prevalence rates of malnutrition at 2.5% to 4% have previously been reported in two tertiary paediatric Australian hospitals. The current study is the first to measure the prevalence of malnutrition, obesity and nutritional risk of paediatric inpatients in multiple hospitals throughout Australia. Methods Malnutrition, obesity and nutritional risk prevalence were investigated in 832 and 570 paediatric inpatients, respectively, in eight tertiary paediatric hospitals and eight regional hospitals across Australia on a single day. Malnutrition and obesity prevalence was determined using z-scores and body mass index (BMI) percentiles. High nutritional risk was determined as a Paediatric Yorkhill Malnutrition Score of 2 or more. Results The prevalence rates of malnourished, wasted, stunted, overweight and obese paediatric patients were 15%, 13.8%, 11.9%, 8.8% and 9.9%, respectively. Patients who identified as Aboriginal and Torres Strait Islander were more likely to have lower height-for-age z-scores (P < 0.01); however, BMI and weight-for-age z-scores were not significantly different. Children who were younger, from regional hospitals or with a primary diagnosis of cardiac disease or cystic fibrosis had significantly lower anthropometric z-scores (P = 0.05). Forty-four per cent of patients were identified as at high nutritional risk and requiring further nutritional assessment. Conclusions The prevalence of malnutrition and nutritional risk of Australian paediatric inpatients on a given day was much higher when compared with the healthy population. In contrast, the proportion of overweight and obese patients was less.

Simulated hyperopic anisometropia and reading, visual information processing, and reading-related eye movement performance in children

Purpose: This study investigated the impact of simulated hyperopic anisometropia and sustained near work on performance of academic-related measures in children. Methods: Participants included 16 children (mean age: 11.1 ± 0.8 years) with minimal refractive error. Academic-related outcome measures included a reading test (Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (Developmental Eye Movement test). Performance was assessed with and without 0.75 D of imposed monocular hyperopic defocus (administered in a randomised order), before and after 20 minutes of sustained near work. Unilateral hyperopic defocus was systematically assigned to either the dominant or non-dominant sighting eye to evaluate the impact of ocular dominance on any performance decrements. Results: Simulated hyperopic anisometropia and sustained near work both independently reduced performance on all of the outcome measures (p<0.001). A significant interaction was also observed between simulated anisometropia and near work (p<0.05), with the greatest decrement in performance observed during simulated anisometropia in combination with sustained near work. Laterality of the refractive error simulation (ocular dominance) did not significantly influence the outcome measures (p>0.05). A reduction of up to 12% in performance was observed across the range of academic-related measures following sustained near work undertaken during the anisometropic simulation. Conclusion: Simulated hyperopic anisometropia significantly impaired academic–related performance, particularly in combination with sustained near work. The impact of uncorrected habitual anisometropia on academic-related performance in children requires further investigation.

Simulated astigmatism impairs academic-related performance in children

Purpose: Astigmatism is an important refractive condition in children. However, the functional impact of uncorrected astigmatism in this population is not well established, particularly with regard to academic performance. This study investigated the impact of simulated bilateral astigmatism on academic-related tasks before and after sustained near work in children. Methods: Twenty visually normal children (mean age: 10.8 ± 0.7 years; 6 males and 14 females) completed a range of standardised academic-related tests with and without 1.50 D of simulated bilateral astigmatism (with both academic-related tests and the visual condition administered in a randomised order). The simulated astigmatism was induced using a positive cylindrical lens while maintaining a plano spherical equivalent. Performance was assessed before and after 20 minutes of sustained near work, during two separate testing sessions. Academic-related measures included a standardised reading test (the Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (the Developmental Eye Movement test). Each participant was systematically assigned either with-the-rule (WTR, axis 180°) or against-the-rule (ATR, axis 90°) simulated astigmatism to evaluate the influence of axis orientation on any decrements in performance. Results: Reading, visual information processing and reading-related eye movement performance were all significantly impaired by both simulated bilateral astigmatism (p<0.001) and sustained near work (p<0.001), however, there was no significant interaction between these factors (p>0.05). Simulated astigmatism led to a reduction of between 5% and 12% in performance across the academic-related outcome measures, but there was no significant effect of the axis (WTR or ATR) of astigmatism (p>0.05). Conclusion: Simulated bilateral astigmatism impaired children’s performance on a range of academic–related outcome measures irrespective of the orientation of the astigmatism. These findings have implications for the clinical management of non-amblyogenic levels of astigmatism in relation to academic performance in children. Correction of low to moderate levels of astigmatism may improve the functional performance of children in the classroom.

Effect of bifocal and prismatic bifocal spectacles on myopia progression in children

Importance Myopia is a significant public health problem, making it important to determine whether a bifocal spectacle treatment involving near prism slows myopia progression in children. Objective To determine whether bifocal and prismatic bifocal spectacles control myopia in children with high rates of myopia progression and to assess whether the treatment effect is dependent on the lag of accommodation and/or near phoria status. Design, Setting, and Participants This 3-year randomized clinical trial was conducted in a private practice. A total of 135 (73 female and 62 male) Chinese-Canadian children (aged 8-13 years; mean [SE] age, 10.29 [0.15] years; mean [SE] myopia, −3.08 [0.10] D) with myopia progression of at least 0.50 D in the preceding year were randomly assigned to 1 of 3 treatments. A total of 128 (94.8%) completed the trial. Interventions Single-vision lenses (control, n = 41), +1.50-D executive bifocals (n = 48), and +1.50-D executive bifocals with 3-Δ base-in prism in the near segment of each lens (n = 46). Main Outcomes and Measures Myopia progression (primary) measured using an automated refractor following cycloplegia and increase in axial length (secondary) measured using ultrasonography at intervals of 6 months for 36 months. Results Myopia progression over 3 years was an average (SE) of −2.06 (0.13) D for the single-vision lens group, −1.25 (0.10) D for the bifocal group, and −1.01 (0.13) D for the prismatic bifocal group. Axial length increased an average (SE) of 0.82 (0.05) mm, 0.57 (0.07) mm, and 0.54 (0.06) mm, respectively. The treatment effect of bifocals (0.81 D) and prismatic bifocals (1.05 D) was significant (P < .001). Both bifocal groups had less axial elongation (0.25 mm and 0.28 mm, respectively) than the single-vision lens group (P < .001). For children with high lags of accommodation (≥1.01 D), the treatment effect of both bifocals and prismatic bifocals was similar (1.1 D) (P < .001). For children with low lags (<1.01 D), the treatment effect of prismatic bifocals (0.99 D) was greater than of bifocals (0.50 D) (P = .03). The treatment effect of both bifocals and prismatic bifocals was independent of the near phoria status. Conclusions and Relevance Bifocal spectacles can slow myopia progression in children with an annual progression rate of at least 0.50 D after 3 years. These results suggest that prismatic bifocals are more effective for myopic children with low lags of accommodation.

Inhibition of form-deprivation myopia by a GABAAOr receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA), in guinea pigs

Purpose To investigate the effects of the relatively selective GABAAOr receptor antagonist (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on form-deprivation myopia (FDM) in guinea pigs. Methods A diffuser was applied monocularly to 30 guinea pigs from day 10 to 21. The animals were randomized to one of five treatment groups. The deprived eye received daily sub-conjunctival injections of 100 μl TPMPA at a concentration of (i) 0.03 %, ( ii) 0.3 %, or (iii) 1 %, a fourth group (iv) received saline injections, and another (v) no injections. The fellow eye was left untreated. An additional group received no treatment to either eye. Prior to and at the end of the treatment period, refraction and ocular biometry were performed. Results Visual deprivation produced relative myopia in all groups (treated versus untreated eyes, P < 0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA, P < 0.0001); myopia was less in deprived eyes receiving either 0.3 % or 1 % TPMPA (saline = −4.38 ± 0.57D, 0.3 % TPMPA = −3.00 ± 0.48D, P < 0.01; 1 % TPMPA = −0.88 ± 0.51D, P < 0.001). The degree of axial elongation was correspondingly less (saline = 0.13 ± 0.02 mm, 0.3 % TPMPA = 0.09 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.02 ± 0.01 mm, P < 0.001) as was the VC elongation (saline = 0.08 ± 0.01 mm, 0.3 % TPMPA = 0.05 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.01 ± 0.01 mm; P < 0.001). ACD and LT were not affected (one-way ANOVA, P > 0.05). One percent TPMPA was more effective at inhibiting myopia than 0.3 % (P < 0.01), and 0.03 % did not appreciably inhibit the myopia (0.03 % TPMPA versus saline, P > 0.05). Conclusions Sub-conjunctival injections of TPMPA inhibit FDM in guinea pig models in a dose-dependent manner.

Configuring retroreflective markings to enhance the night-time conspicuity of road workers

This study investigated whether the night-time conspicuity of road workers can be enhanced by positioning retroreflective strips on the moveable joints in patterns that convey varying degrees of biological motion. Participants were 24 visually normal adults (12 young M = 26.8 years; 12 older M = 72.9 years). Visual acuity, contrast sensitivity and glare sensitivity were recorded for each participant. Experimenters acting as road workers walked in place on a closed road circuit within simulated road work sites, facing either the oncoming driver or the roadway (presenting sideways to the driver) and wearing one of four clothing conditions: (i) standard road worker vest; (ii) standard vest plus thigh-mounted retroreflective strips; (iii) standard vest plus retroreflective strips on ankles and knees; (iv) standard vest plus retroreflective strips positioned on the extremities in a configuration that conveyed biological motion (“biomotion”). As they drove along the closed road participants were instructed to press a button to indicate when they first recognized that a road worker was present. The results demonstrated that regardless of the direction of walking, road workers wearing biomotion clothing were recognized at significantly (p < 0.05) longer distances (3×), relative to the standard vest alone. Response distances were significantly shorter for the older drivers. Contrast sensitivity was a better predictor of the ability to recognize road workers than was visual acuity or glare sensitivity. We conclude that adding retroreflective strips in the biomotion configuration can significantly improve road worker conspicuity regardless of the road worker's orientation and the age of the driver.

Differential effects of refractive blur on day and night-time driving performance

Purpose To investigate the effect of different levels of refractive blur on real-world driving performance measured under day and nighttime conditions. Methods Participants included 12 visually normal, young adults (mean age = 25.8 ± 5.2 years) who drove an instrumented research vehicle around a 4 km closed road circuit with three different levels of binocular spherical refractive blur (+0.50 diopter sphere [DS], +1.00 DS, +2.00 DS) compared with a baseline condition. The subjects wore optimal spherocylinder correction and the additional blur lenses were mounted in modified full-field goggles; the order of testing of the blur conditions was randomized. Driving performance was assessed in two different sessions under day and nighttime conditions and included measures of road signs recognized, hazard detection and avoidance, gap detection, lane-keeping, sign recognition distance, speed, and time to complete the course. Results Refractive blur and time of day had significant effects on driving performance (P < 0.05), where increasing blur and nighttime driving reduced performance on all driving tasks except gap judgment and lane keeping. There was also a significant interaction between blur and time of day (P < 0.05), such that the effects of blur were exacerbated under nighttime driving conditions; performance differences were evident even for +0.50 DS blur relative to baseline for some measures. Conclusions The effects of blur were greatest under nighttime conditions, even for levels of binocular refractive blur as low as +0.50 DS. These results emphasize the importance of accurate and up-to-date refractive correction of even low levels of refractive error when driving at night.

Seeing pedestrians at night : effect of driver age and visual abilities

Purpose To quantify the effects of driver age on night-time pedestrian conspicuity, and to determine whether individual differences in visual performance can predict drivers' ability to recognise pedestrians at night. Methods Participants were 32 visually normal drivers (20 younger: M = 24.4 years ± 6.4 years; 12 older: M = 72.0 years ± 5.0 years). Visual performance was measured in a laboratory-based testing session including visual acuity, contrast sensitivity, motion sensitivity and the useful field of view. Night-time pedestrian recognition distances were recorded while participants drove an instrumented vehicle along a closed road course at night; to increase the workload of drivers, auditory and visual distracter tasks were presented for some of the laps. Pedestrians walked in place, sideways to the oncoming vehicles, and wore either a standard high visibility reflective vest or reflective tape positioned on the movable joints (biological motion). Results Driver age and pedestrian clothing significantly (p < 0.05) affected the distance at which the drivers first responded to the pedestrians. Older drivers recognised pedestrians at approximately half the distance of the younger drivers and pedestrians were recognised more often and at longer distances when they wore a biological motion reflective clothing configuration than when they wore a reflective vest. Motion sensitivity was an independent predictor of pedestrian recognition distance, even when controlling for driver age. Conclusions The night-time pedestrian recognition capacity of older drivers was significantly worse than that of younger drivers. The distance at which drivers first recognised pedestrians at night was best predicted by a test of motion sensitivity.

The effect of topical adrenergic and anticholinergic agents on the choroidal thickness of young healthy adults

The human choroid is capable of rapidly changing its thickness in response to a variety of stimuli. However little is known about the role of the autonomic nervous system in the regulation of the thickness of the choroid. Therefore, we investigated the effect of topical parasympatholytic and sympathomimetic agents upon the choroidal thickness and ocular biometrics of young healthy adult subjects. Fourteen subjects (mean age 27.9 ± 4 years) participated in this randomized, single-masked, placebo-controlled study. Each subject had measurements of choroidal thickness (ChT) and ocular biometrics of their right eye taken before, and then 30 and 60 min following the administration of topical pharmacological agents. Three different drugs: 2% homatropine hydrobromide, 2.5% phenylephrine hydrochloride and a placebo (0.3% hydroxypropyl methylcellulose) were tested in all subjects; each on different days (at the same time of the day) in randomized order. Participants were masked to the pharmacological agent being used at each testing session. The instillation of 2% homatropine resulted in a small but significant increase in subfoveal ChT at 30 and 60 min after drug instillation (mean change 7 ± 3 μm and 14 ± 2 μm respectively; both p < 0.0001). The parafoveal choroid also exhibited a similar magnitude, significant increase in thickness with time after 2% homatropine (p < 0.001), with a mean change of 7 ± 0.3 μm and 13 ± 1 μm (in the region located 0.5 mm from the fovea center), 6 ± 1 μm and 12.5 ± 1 μm (1 mm from the fovea center) and 6 ± 2 μm and 12 ± 2 μm (1.5 mm from the fovea center) after 30 and 60 min respectively. Axial length decreased significantly 60 min after homatropine (p < 0.01). There were also significant changes in lens thickness (LT) and anterior chamber depth (ACD) (p < 0.05) associated with homatropine instillation. No significant changes in choroidal thickness, or ocular biometrics were found after 2.5% phenylephrine or placebo at any examination points (p > 0.05). In human subjects, significant increases in subfoveal and parafoveal choroidal thickness occurred after administration of 2% homatropine and this implies an involvement of the parasympathetic system in the control of choroidal thickness in humans.

Factors influencing Saudi Arabian optometry candidates' career choices and institution of learning. Why do Saudi students choose to study optometry?

Optometry is a primary health-care profession (PHCP) and this study aimed to elucidate the factors influencing the choice of optometry as a career for Saudi students, the students' perceptions of optometry and the effect of gender. METHODS Two hundred and forty-seven students whose average age was 21.7 ± 1.5 (SD) years and who are currently enrolled in two colleges of optometry in Saudi Arabia--King Saud University (KSU) and Qassim University (QU)--completed self-administered questionnaires. The survey included questions concerning demography, career first choice, career perception and factors influencing career choices. RESULTS The response rate was 87.6 per cent and there were 161 male (64.9 per cent) students. Seventy-nine per cent of the participants were from KSU (males and females) and 20.6 per cent were from QU (only males). Seventy-three per cent come from Riyadh and 19 per cent are from Qassim province. Regarding the first choice for their careers, the females (92 per cent) were 0.4 times more likely (p = 0.012) to choose optometry than males (78.3 per cent). The males were significantly more likely to be influenced by the following factors: the Doctor of Optometry (OD) programs run at both universities, good salary and prospects (p < 0.05, for all). The women were significantly less likely to be influenced by another individual (p = 0.0004). Generally, more than two-thirds of the respondents viewed the desire to help others, professional prestige and the new OD programs as the three most influential factors in opting for a career in optometry. CONCLUSION Females were more likely to opt for a career in optometry and males were more likely to be influenced by the new OD programs, good salary and job prospects. Service provision to others in the community was a primary motivation to opt for a career in optometry among young Saudis.

Fully automated, semiautomated, and manual morphometric analysis of corneal subbasal nerve plexus in individuals with and without diabetes

Purpose The aim of the study was to determine the association, agreement, and detection capability of manual, semiautomated, and fully automated methods of corneal nerve fiber length (CNFL) quantification of the human corneal subbasal nerve plexus (SNP). Methods Thirty-three participants with diabetes and 17 healthy controls underwent laser scanning corneal confocal microscopy. Eight central images of the SNP were selected for each participant and analyzed using manual (CCMetrics), semiautomated (NeuronJ), and fully automated (ACCMetrics) software to quantify the CNFL. Results For the entire cohort, mean CNFL values quantified by CCMetrics, NeuronJ, and ACCMetrics were 17.4 ± 4.3 mm/mm2, 16.0 ± 3.9 mm/mm2, and 16.5 ± 3.6 mm/mm2, respectively (P < 0.01). CNFL quantified using CCMetrics was significantly higher than those obtained by NeuronJ and ACCMetrics (P < 0.05). The 3 methods were highly correlated (correlation coefficients 0.87–0.98, P < 0.01). The intraclass correlation coefficients were 0.87 for ACCMetrics versus NeuronJ and 0.86 for ACCMetrics versus CCMetrics. Bland–Altman plots showed good agreement between the manual, semiautomated, and fully automated analyses of CNFL. A small underestimation of CNFL was observed using ACCMetrics with increasing the amount of nerve tissue. All 3 methods were able to detect CNFL depletion in diabetic participants (P < 0.05) and in those with peripheral neuropathy as defined by the Toronto criteria, compared with healthy controls (P < 0.05). Conclusions Automated quantification of CNFL provides comparable neuropathy detection ability to manual and semiautomated methods. Because of its speed, objectivity, and consistency, fully automated analysis of CNFL might be advantageous in studies of diabetic neuropathy.

Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes : Development of a potential measure of diabetic peripheral neuropathy

Purpose To investigate longitudinal changes of subbasal nerve plexus (SNP) morphology and its relationship with conventional measures of neuropathy in individuals with diabetes. Methods A cohort of 147 individuals with type 1 diabetes and 60 age-balanced controls underwent detailed assessment of clinical and metabolic factors, neurologic deficits, quantitative sensory testing, nerve conduction studies and corneal confocal microscopy at baseline and four subsequent annual visits. The SNP parameters included corneal nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL) and were quantified using a fully-automated algorithm. Linear mixed models were fitted to examine the changes in corneal nerve parameters over time. Results At baseline, 27% of the participants had mild diabetic neuropathy. All SNP parameters were significantly lower in the neuropathy group compared to controls (P<0.05). Overall, 89% of participants examined at baseline also completed the final visit. There was no clinically significant change to health and metabolic parameters and neuropathy measures from baseline to the final visit. Linear mixed model revealed a significant linear decline of CNFD (annual change rate, -0.9 nerve/mm2, P=0.01) in the neuropathy group compared to controls, which was associated with age (β=-0.06, P=0.04) and duration of diabetes (β=-0.08, P=0.03). In the neuropathy group, absolute changes of CNBD and CNFL showed moderate correlations with peroneal conduction velocity and cold sensation threshold, respectively (rs, 0.38 and 0.40, P<0.05). Conclusion This study demonstrates dynamic small fiber damage at the SNP, thus providing justification for our ongoing efforts to establish corneal nerve morphology as an appropriate adjunct to conventional measures of DPN.