Latency of the pupil light reflex: sample rate, stimulus intensity, and variation in normal subjects

PURPOSE. To investigate the clinical usefulness of the latency of the pupil light reflex by optimizing its measurement, characterizing its variability, and determining the sensitivity of pupil latency as a function of stimulus input in normal subjects. METHODS. Computerized binocular infrared pupillography was performed in 14 eyes of seven healthy subjects. Pupils were recorded simultaneously at 60 and 1000 Hz. Each eye was alternatively stimulated eight times for 50 ms every 2.5 seconds, increasing by 0.5 log units over a 2.0-log-unit range. To determine intersubject and intereye variability, 98 eyes of 49 healthy subjects were recorded at 60 Hz over a 3.0-log-unit range (15°radius stimulation, four repetitions at each intensity). RESULTS. Accuracy and resolution of latency were limited by the number of light reflexes used to estimate the average latency and were significantly affected by sampling rate when the number of reflexes recorded was fewer than four. Binocular recording and interpolation of the 60-Hz recording to 300 Hz added resolution to the latency. Biological variability contributed more to interindividual variability than did measurement variability. The range of intereye afferent asymmetry of latency in normal subjects was only between 8.3 and 35 ms-less with brighter stimulus intensity. CONCLUSIONS. An optimal method for determination of the onset of the pupil light reflex was devised that consisted of filtering, interpolation of pupil recordings, and analysis of the first and second derivative of the pupil movement. Most of the variability in latency as a function of intensity in normal subjects was due to interindividual variation and latency was well matched between the two eyes of the subjects. (Invest Ophthalmol Vis Sci. 2003;44:1546 -155

Functional Characterization of Retina and Optic Nerve after Acute Ocular Ischemia in Rats

purpose. To functionally characterize the status of the rat retina and optic nerve after acute elevation of intraocular pressure (IOP) and to determine the dynamics of the pathologic changes in the ischemic retina and optic nerve. methods. Retinal ischemia was induced in rats by acutely increasing the IOP (110 mm Hg/60 minutes). Direct and indirect pupil light reflexes (PLRs) were recorded from the noninjured eye, and electroretinograms (flash and flicker ERG) were recorded from the injured and control eyes before and after surgery. Amplitudes and latencies were calculated for each recording session. results. Preoperative PLRratios (indirect/direct PLR) were 76.7 ± 2.6 (mean ± SEM). Twenty-four hours after surgery the PLRratio was 15.2 ± 12.8, 10 days after surgery, 11.6 ± 9.8; 20 days after surgery, 26.5 ± 8.0; and 28 days after surgery, 33.27 ± 9.3. However, at day 35, the PLR had significantly recovered (41.1 ± 7.3) when compared with the 24-hour postoperative ratios (P \u3c 0.01, repeated-measures ANOVA). Forty-two days after surgery, the PLRratio started to decrease once again in the injured eyes (28.7 ± 5.9). Electroretinographic amplitudes (full-field flash ERG) followed a similar pattern. Cone responses (flicker ERG) were measured 42 days after surgery and revealed defects in injured eyes (control eyes: 46.6 ± 2.9 μV, injured eyes: 3.4 ± 1.7 μV). Histologic analysis revealed ischemic damage to all retinal layers, with the primary defects localized to the central retina. conclusions. Acute ocular ischemia causes a significant decrease in retinal function, as measured by PLR and ERG, although over time the rat retina and optic nerve show partial regain of function

Optical coherence tomography in multiple sclerosis: A 3-year prospective multicenter study

Prospective multicenter study; Multiple sclerosis; TomographyEstudi prospectiu multicèntric; Esclerosi múltiple; TomografiaEstudio multicéntrico prospectivo; Esclerosis múltiple; TomografíaObjective To evaluate changes over 3 years in the thickness of inner retinal layers including the peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (mGCIPL), in individuals with relapsing-remitting multiple sclerosis (RRMS) versus healthy controls; to determine whether optical coherence tomography (OCT) is sufficiently sensitive and reproducible to detect small degrees of neuroaxonal loss over time that correlate with changes in brain volume and disability progression as measured by the Expanded Disability Status Scale (EDSS). Methods Individuals with RRMS from 28 centers (n = 333) were matched with 64 healthy participants. OCT scans were performed on Heidelberg Spectralis machines (at baseline; 1 month; 6 months; 6-monthly thereafter). Results OCT measurements were highly reproducible between baseline and 1 month (intraclass correlation coefficient >0.98). Significant inner retinal layer thinning was observed in individuals with multiple sclerosis (MS) compared with controls regardless of previous MS-associated optic neuritis––group differences (95% CI) over 3 years: pRNFL: −1.86 (−2.54, −1.17) µm; mGCIPL: −2.03 (−2.78, −1.28) µm (both p 5 years (pRNFL: p < 0.05; mGCIPL: p < 0.01). Brain volume decreased by 1.3% in individuals with MS over 3 years compared to 0.5% in control subjects (effect size 0.76). mGCIPL atrophy correlated with brain atrophy (p < 0.0001). There was no correlation of OCT data with disability progression. Interpretation OCT has potential to estimate rates of neurodegeneration in the retina and brain. The effect size for OCT, smaller than for magnetic resonance imaging based on Heidelberg Spectralis data acquired in this study, was increased in early disease.The authors wish to thank Carolyn M. Ervin for her substantial contribution in the data analyses, as well as Mark Kirby, Aisling Towell, and Marie-Catherine Mousseau (Novartis Ireland Ltd.) for their writing support, funded by Novartis Pharma AG, Basel, Switzerland. FB is supported by the NIHR biomedical research center at UCLH

Evaluation of retinal status using chromatic pupil light reflex activity in healthy and diseased canine eyes

purpose. To differentiate rod-cone–mediated pupil light reflexes (PLRs) from intrinsic melanopsin-mediated pupil light reflexes by comparing pupil responses with red and blue light stimuli of differing intensities in normal dog eyes and in those with sudden acquired retinal degeneration syndrome (SARDS) exhibiting a nonrecordable electroretinogram. methods. The PLR was evaluated in 14 healthy dogs using a computerized pupillometry system and in five dogs with SARDS. Contraction amplitude, velocity, and implicit time of the PLR were studied as a function of peak wavelength (480 nm vs. 630 nm) and light intensity (−0.29 to 5.3 log units) to determine characteristics of the rod-cone versus predominantly melanopsin-mediated PLR activity. results. The PLR in healthy, mildly sedated dogs could be elicited at low light intensities (−0.29 log units; 0.51 cd/m2). Canine SARDS patients displayed a complete absence of vision, electroretinographic amplitude, and PLR at low light intensity. However, in SARDS dogs, a pupil light reflex could be elicited with wavelengths corresponding to the melanopsin spectral sensitivity (blue light − peak at 480 nm) and at relatively high intensity (4.3 log units or higher), whereas red light (630 nm peak wavelength) was ineffective in eliciting any detectable PLR response even at light intensities of 6 log units (1,000,000 cd/m2). conclusions. The PLR in healthy canine eyes can be elicited at very low light intensities using red and blue wavelengths of light, but in dogs with blindness caused by SARDS, the pupil reacts only to high-intensity blue wavelength light, implying loss of the rod-cone–mediated PLR and most likely the presence of intrinsic, melanopsin-mediated, retinal ganglion cell–mediated PLR.This article is from Investigative Ophthalmology & Visual Science 48 (2007): 5178, doi: 10.1167/iovs.07-0249.</p

Patterns of Distribution of Oxygen-Binding Globins, Neuroglobin and Cytoglobin in Human Retina

Objective To determine the distribution of 2 intracellular oxygen-carrying molecules, neuroglobin (NGB) and cytoglobin (CYGB), in specific retinal cell types of human retinas. Methods Specific antibodies against NGB and CYGB were used in immunohistochemical studies to examine their distribution patterns in human retinal sections. Double-labeling studies were performed with the anti-NGB and anti-CYGB antibodies along with antibodies against neuronal (microtubule-associated protein 2, class III β-tubulin [TUJ1], protein kinase C alpha, calretinin) and glial (vimentin, glial fibrillary acid protein) markers. Confocal microscopy was used to examine the retinal sections. Results Immunohistochemical analysis of human retinal tissue showed NGB and CYGB immunoreactivity in the ganglion cell layer, inner nuclear layer, inner and outer plexiform layers, and retinal pigment epithelium. Neuroglobin immunoreactivity was also present in the outer nuclear layer and photoreceptor inner segments. Neuroglobin and CYGB were coexpressed in the neurons in the ganglion cell layer and inner nuclear layer but not within glial cells. Conclusion Neuroglobin and CYGB are colocalized within human retinal neurons and retinal pigment epithelium but not within glial cells. Clinical Relevance Our results suggest that NGB and CYGB may serve a neuroprotective role as scavengers of reactive oxygen species and therefore should be considered when developing therapeutic strategies for treatment of hypoxia-related ocular diseases

Effect of Treatment with Salsalate, Menhaden Oil, Combination of Salsalate and Menhaden Oil, or Resolvin D1 of C57Bl/6J Type 1 Diabetic Mouse on Neuropathic Endpoints

Aims. In this study a streptozotocin induced type 1 diabetes mouse model was used to assess the effectiveness of salsalate, menhaden oil, the combination of salsalate and menhaden oil, or resolvin D1 on neuropathic endpoints. Materials and Methods. Changes in body weight, blood glucose, serum markers for triglycerides, free fatty acids, cholesterol, and resolvin D1, motor and sensory nerve conduction velocities and thermal sensitivity were assessed, as well as performing in vivo confocal microscopy of subepithelial corneal nerves and immunohistochemistry of nerves in the cornea and foot pad. Results. Diabetic animals failed to gain weight and had elevated blood glucose levels. Diabetic mice had slowed nerve conduction velocity, reduced innervation of the foot pad and cornea subepithelial and epithelial layers, and reduced thermal sensitivity. Monotherapy treatment with salsalate, menhaden oil, and resolvin D1 reduced the pathological signs of diabetic neuropathy. The combination of salsalate and menhaden oil also reduced signs of pathology and generated elevated plasma levels of resolvin D1 compared to other groups. Conclusions. Additional studies are needed to determine whether the combination of salsalate and menhaden oil may be more efficacious than monotherapy alone for the treatment of diabetic peripheral neuropathy