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Biomedical subjects

Randy H Kardon

Publications and source records attributed to Randy H Kardon.

At least 19 recordsLinked to original sources

Quantifying axonal loss after optic neuritis with optical coherence tomography.

OBJECTIVE: To determine to what degree changes in retinal nerve fiber layer (RNFL) thickness after optic neuritis (ON) correlate with either visual recovery or impairment. METHODS: ON can cause visible defects within the RNFL, which can be quantified using optical coherence tomography (OCT). It may be possible to predict visual recovery by measuring RNFL loss after ON. Fifty-four patients underwent repeated evaluations with optical coherence tomography and standardized ophthalmic testing after ON. Regression analyses were used to determine the relationship between RNFL thickness and visual function. RESULTS: Thinning of the RNFL was seen in the majority of patients (74%), and it tended to occur within 3 to 6 months of ON. The average RNFL value was thinner (p<0.0001) in the affected (78 microm) compared with the unaffected eye (100 microm). Patients with incomplete visual recovery demonstrated greater RNFL loss after ON. Regression analyses demonstrated a threshold of RNFL thickness (75 microm), below which RNFL measurements predicted persistent visual dysfunction. INTERPRETATION: Determination of RNFL thickness may predict visual recovery after ON, and lower RNFL values correlate with impaired visual function. Optical coherence tomography may have a potential role as a surrogate marker for axonal integrity within the optic nerve among patients with ON.

Adolescent↗

Subretinal neovascular membrane in idiopathic intracranial hypertension.

PURPOSE: To define the prevalence, natural history, treatment, and prognosis of papilledema-related juxtapapillary subretinal neovascular membranes (SRNVMs). DESIGN: Retrospective observational case series. METHODS: We conducted a retrospective chart review. RESULTS: Of 1140 cases of idiopathic intracranial hypertension, six patients had juxtapapillary SRNVM. Three patients were observed, and their final visual acuities were 20/20, 20/50, and 20/200. Three SRNVM involved the fovea; two of the cases were treated with argon laser therapy, and one case was treated with photodynamic therapy. CONCLUSION: SRNVM in idiopathic intracranial hypertension is rare (0.53%). Most cases of juxtapapillary SRNVM are self-limited and regress, can be observed, and have a favorable visual prognosis. The progression of the SRNVM ophthalmoscopically or angiographically toward the fovea, however, might be an indication for laser treatment. Once subfoveal extension occurs, the visual outcome tends to be unfavorable. No patients had recurrence of SRNVM after the resolution of the papilledema.

Acetazolamide↗

Irene E. Loewenfeld, PhD Physiologist of the pupil.

Irene E. Loewenfeld, PhD has devoted a long and vigorous professional life to understanding the workings of the pupil of the human eye. Her interest in the pupil began in 1940 when she went to work as a technician in the pupillography laboratory of Professor Otto Lowenstein at New York University. It culminated in her widely admired textbook The Pupil, published in 1993. Among her many contributions, Loewenfeld provided rigorous observations about Adie tonic pupil, anisocoria in optic tract lesions, Argyll Robertson pupil, oculomotor paresis with cyclic spasms, and innovations in electronic recordings of pupil movement.

History, 20th Century↗

The Argyll Robertson pupil.

The Argyll Robertson (AR) pupil has been defined as a pupil that is small and constricts poorly to direct light but briskly when a target within reading distance is viewed ("light-near dissociation"). Most descriptions of the AR pupil do not mention segmental iris sphincter constriction, or slow, sustained constriction with a near vision effort. Such features are considered typical of the light-near dissociation of Adie syndrome and of neuropathic tonic pupils, where damage to the ciliary ganglion or ciliary nerves is believed to be the mechanism. Because the AR pupil lacks these features, it has been attributed to a dorsal midbrain lesion that interrupts the pupillary light reflex pathway but spares the more ventral pupillary near reflex pathway. However, lesions in this region have not been reliably demonstrated in syphilis. Resolving the issue about the location of the syphilitic lesion that produces the AR pupil will depend on careful examination of patients with techniques designed to disclose segmental palsy of the iris. If segmental iris sphincter palsy is found and the light-near dissociation has tonic features, one must conclude that the mechanism of the pupil disorder is a ciliary (peripheral) rather than a midbrain (central) denervation. Until better evidence settles the localization of the AR pupil, it is appropriate to screen patients with bilateral tonic pupils for syphilis.

Humans↗

Neuroglobin and cytoglobin: oxygen-binding proteins in retinal neurons.

PURPOSE: The goal of this study was to describe the detailed localization of the novel oxygen-binding molecules, neuroglobin (Ngb) and cytoglobin (Cygb), in mammalian retinas and to determine whether Ngb and Cygb are neuronal or glial proteins in the retina. METHODS: Antibodies directed against Ngb and Cygb were used to examine their patterns of distribution in normal canine retinas. Immunoblot analysis was performed to verify antibody specificity and the presence of Ngb and Cygb in canine tissues. Double-labeling immunohistochemistry was performed with the Ngb and Cygb antibodies along with antibodies against neuronal (MAP-2, class III beta-tubulin (TUJ1), PKCalpha, and calretinin) and glial antigens (vimentin and CRALBP). Tissue sections were analyzed with light and confocal microscopy. RESULTS: Ngb and Cygb proteins were observed in different retinal cells. Cygb (but not Ngb) was also present in canine kidney, liver, lung, and heart tissue. Immunohistochemical analysis of canine retinas demonstrated Ngb immunoreactivity (IR) in the ganglion cell layer (GCL), inner (INL) and outer (ONL) nuclear layers, inner (IPL) and outer plexiform (OPL) layers, photoreceptor inner segments (IS), and retinal pigment epithelium (RPE). Ngb IR was localized within retinal neurons, but not in glia. Cygb IR was found in neurons and their processes in the GCL, IPL, INL, and OPL and within the RPE, but not in glia. CONCLUSIONS: Ngb and Cygb are widely distributed in retinal neurons and RPE, but not in glial cells of the canine retina. Their structure and distribution is suggestive of a possible role in oxygen transport in the mammalian retina.

Animals↗

Morphological integration and functional assessment of transplanted neural progenitor cells in healthy and acute ischemic rat eyes.

We have functionally and morphologically characterized the retina and optic nerve after neural progenitor cell transplants to healthy rat eyes and eyes damaged by acute elevation of intraocular pressure (IOP). Green fluorescent protein-expressing adult rat hippocampal progenitor cells (AHPCs) were transplanted by intravitreal injection into healthy eyes and eyes damaged with acute ocular hypertension. Pupil light reflexes (PLR) and electroretinograms (ERGs) were recorded preoperatively and postoperatively. Eyes were subsequently prepared for immunohistochemical analysis and confocal imaging. Transplanted AHPCs were found in 8 of 15 (53%) acute ischemic eyes 62 days after surgery and 5 of 10 (50%) healthy eyes 32 days after grafting. Analysis of PLR and ERG function in acute ischemic eyes revealed no statistically significant difference compared to controls after transplantation for all observed functional parameters. Transplant into healthy rat eyes revealed no PLR or ERG amplitude deficits between transplanted and non-transplanted (control) eyes. Morphological and immunohistochemical analysis revealed that transplanted AHPCs survived and differentiated in both normal and injured retinal environments. Morphological integration occurred primarily within the inner retinal layers of the acute ischemic eyes. AHPCs were found to express neuronal and glial markers following transplantation. Transplanted AHPCs have the ability to integrate and differentiate in ischemia damaged retinas. PLR and ERG analysis revealed no significant difference in functional outcome in transplant recipient eyes.

Acute Disease↗

The use of acetazolamide in idiopathic intracranial hypertension during pregnancy.

PURPOSE: To describe the pregnancy outcomes after the use of acetazolamide in pregnant patients with idiopathic intracranial hypertension (IIH). DESIGN: Observational case series. METHODS: setting: Two tertiary care academic neuro-ophthalmology units. patient population: Patients with IIH treated with acetazolamide. observation procedure: Documentation of pregnancy outcome. main outcome measures: Normal pregnancy, fetal loss, or congenital malformation. RESULTS: Twelve patients were treated with acetazolamide for IIH during pregnancy, and there were no adverse pregnancy outcomes. A critical review of the English language literature on the subject failed to demonstrate any convincing evidence for any adverse effect on pregnancy for acetazolamide. CONCLUSIONS: Acetazolamide at high doses may produce birth defects in animals, but there is little clinical or experimental evidence to support any adverse effect of the drug on pregnancy outcomes in humans. If the clinical situation warrants the use of acetazolamide in IIH, then the drug probably can be offered after appropriate informed consent.

Acetazolamide↗

The diagnostic yield of the evaluation for isolated unexplained optic atrophy.

PURPOSE: To report the diagnostic yield for the evaluation of isolated and unexplained optic atrophy. SETTING: Two tertiary care academic neuroophthalmology clinics. DESIGN: Retrospective case series. PARTICIPANTS: Patients with optic atrophy. METHODS: Retrospective review of all charts with the diagnosis of optic atrophy. Included patients were adults with isolated, but unexplained, optic atrophy. Patients were excluded if they were children, had incomplete or inadequate documentation of the findings, had nonneurologically isolated optic atrophy (e.g., other localizing findings), or had a history (e.g., prior neuroimaging study showed a compressive lesion, prior ischemic optic neuropathy) or examination (e.g., central retinal artery occlusion) evidence for an etiology for the optic atrophy. MAIN OUTCOME MEASURE: Results of diagnostic evaluation. RESULTS: A total of 1110 charts with the diagnosis of optic atrophy were reviewed from the 2 participating institutions (368 from the University of Cincinnati and 742 from the University of Iowa). Of these 1110 charts, 91 (8%) with isolated unexplained optic atrophy were included, and 1019 charts (92%) were excluded. Of 91 included patients, 18 (20%) had a compressive lesion causing optic atrophy, and 73 (80%) cases had no etiology for the optic atrophy on neuroimaging. Of the 18 patients with abnormal imaging (e.g., meningioma, pituitary adenoma, craniopharyngioma) studies, 11 had bilateral and 7 had unilateral optic atrophy. Five of the 18 patients had progressive visual loss, 3 had hemianopic visual field loss, and 11 were younger than 50 years old. CONCLUSIONS: Patients with optic atrophy in our study typically had historical or examination findings that led to an etiologic diagnosis. Neuroimaging showed an etiology in 20% of patients. Other laboratory testing did not produce an etiologic diagnosis in the absence of a suggestive history or examination. On the basis of our results, we recommend neuroimaging for all patients with unexplained optic atrophy and consideration for directed laboratory studies only.

Brain Neoplasms↗

Presumed "sulfa allergy" in patients with intracranial hypertension treated with acetazolamide or furosemide: cross-reactivity, myth or reality?

PURPOSE: To determine whether acetazolamide or furosemide produce allergic cross-reactions in patients with self-reported "sulfa allergy." DESIGN: Retrospective case series. METHODS: A retrospective review included patients with intracranial hypertension and a self-reported sulfa allergy treated with either acetazolamide or furosemide seen at the University of Iowa Hospitals and Clinics from 1972 to 2003. All presumed medication-related side effects were collected, including both predictable adverse effects (for example, paresthesias, fatigue) and unpredictable adverse reactions (for example, cutaneous fixed eruptions, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, anaphylaxis). RESULTS: We reviewed 363 charts. Of these, 329 patients (91%) were excluded. Of the remaining 34 cases that did report a so-called sulfa allergy, 13 (38%) received acetazolamide alone, 7 (21%) received furosemide alone, and 14 (41%) received both acetazolamide and furosemide. Of the 27 patients who received acetazolamide, 10 (37%) had no documented allergic cross-reaction to sulfa, and 2 (7%) cases had urticaria. The remaining 15 (56%) of acetazolamide-treated patients experienced predictable adverse reactions for this drug (for example, paresthesias). No patient experienced a severe allergic cross-reaction to sulfa. Of 21 patients who received furosemide, no unpredictable adverse reactions or allergic cross-reactions to sulfa were noted. CONCLUSIONS: We find little clinical or pharmacological evidence to suggest that a self-reported sulfa allergy is likely to produce a life-threatening cross-reaction with acetazolamide or furosemide. These medications should be considered for intracranial hypertension if the risk-to-benefit ratio warrants their use.

Acetazolamide↗

Functional evaluation of retina and optic nerve in the rat model of chronic ocular hypertension.

PURPOSE: To functionally characterize the rat retina and optic nerve after chronic elevation of the intraocular pressure (IOP) using electroretinography (ERG) and computerized pupillometry. METHODS: Chronic elevation of the IOP was induced in Brown Norway rats by combined injection of indocyanine green dye (ICG) into the anterior chamber and diode laser treatment, followed by ERG and pupil light reflex (PLR) monitoring. RESULTS: Laser treatment induced significant elevation of the IOP in operated eyes for 6 weeks, with maximal values observed 14 days postoperatively (ctrl=18.4+/-2.4 and operated=35+/-8.4 mmHg; mean+/-sd). Preoperative values for the PLR(ratio) were 68.5+/-4% (mean+/-sem; %). Three days postoperatively the PLR(ratio) decreased to 60.3+/-10.3%, but was not significantly different compared to preoperative values (p > 0.05 Kruskal-Wallis non-parametric test with Dunn's post-test). However, 7, 14 and 21 days postoperatively the PLR function dramatically decreased to 14.6+8.6, 11.5+/-6.7 and 12.6+/-4%, respectively, and was significantly smaller compared to preoperative values (p < 0.01). At day 28 the PLR significantly recovered and was not significantly different compared to preoperative values (PLR(ratio)=38.5+/-8.6, p > 0.05). However, 35 days after surgery the PLR started to decrease once again in the operated eyes (PLR(ratio)=17.2+/-7.4%) and was significantly smaller again compared to preoperative values (p < 0.05) The PLR values continued to decrease until the end of experiment (60 days postoperatively). ERG analysis of operated eyes revealed significantly decreased amplitudes of a- and b-waves 10d postoperatively, while oscillatory potentials (OPs) and flicker ERG (flERG) amplitudes were not detectable. However, 28 days postoperatively OPs significantly, but temporarily recovered, while a-wave, b-wave and flERG amplitudes did not significantly change compared to values observed 10d postoperatively. The ERG analysis of the operated eyes revealed significantly reduced amplitudes 60 days postoperatively. Histological analysis revealed degeneration of all retina layers and optic nerve axons. CONCLUSIONS: Chronic ocular hypertension in rats produces dramatic damage to all retinal layers and optic nerves observed by morphological and functional methods which significantly correlate with the IOP elevation. Outer retina of glaucomatous rats seems to be more susceptible to the damage due to chronic elevation of the IOP. Chronic hypertensive rat eyes have capacity to temporarily recover function of the inner retina and optic nerve.

Animals↗

An objective method to define outlier optical coherence tomograms and repeatability of retinal nerve fibre layer measurements.

PURPOSE: To compare the variation in thickness and reflectivity of the retinal nerve fibre layer (RNFL), circumferentially and on repeated testing. METHODS: In 24 normal eyes and 38 eyes with different optic neuropathies or retinopathies, third-party optical coherence tomography (OCT) software defined the RNFL border based on the reflectivity pattern across the retina and also provided measurements of the mean reflectivity and total retinal thickness in addition to RNFL thickness. A new Gaussian filtering method was implemented so that the weight of the applied filter was varied for each of five individually repeated scans until an optimum weight filter was determined. RESULTS: The scans requiring the highest weight filter could be identified as 'outlier' scans that contained measurement or alignment artifacts. There was no difference in the weights of filtering needed for normal and abnormal eyes. The RNFL thickness and reflectivity, and retinal thickness were highly correlated with one another in normal and abnormal eyes. CONCLUSIONS: A new Gaussian filtering routine was devised that not only defined the most reproducible substructure of the RNFL for a given patient's eye, but also provided a new method of quantifying measurement variability and identification of scans with measurement or alignment artifacts.

Adult↗

Temporary elevation of the intraocular pressure by cauterization of vortex and episcleral veins in rats causes functional deficits in the retina and optic nerve.

PURPOSE: To evaluate visual function in rats with chronic elevation of intraocular pressure (IOP). METHODS: Chronic ocular hypertension was induced in the left eye of 14 adult Brown Norway rats by cauterizing 3 vortex veins and 2 major episcleral veins; the right eye served as a non-operated control. A control group (n=5) was sham operated on the left eye. Prior to surgery, the IOP was measured with a Tonopen, the pupil light reflex (PLR) evaluated with a custom-made computerized pupillometer and electroretinograms (ERGs) were recorded simultaneously from both eyes post surgically: IOP was measured on weeks 1, 3, 5 and 8 post-operatively, pupil light reflexes on weeks 1, 4 and 8 post-operatively, and ERGs on weeks 4 and 8 post-operatively. Sixty five days postoperatively, rats were euthanized and optic nerves and eye globes were prepared for histological analysis. RESULTS: Seven days after surgery 5/14 rats developed significant elevation of the IOP in operated eyes (control eyes: 25.1+/-0.5mmHg; operated eyes: 34.1+/-0.6mmHg; mean+/-SEM; p=0.0004; Paired t-test). Elevation of the IOP was sustained at 3 (p=0.002) and 5 (p=0.007) weeks postoperatively. However, IOP values did not significantly differ between control and operated eyes 8 weeks postoperatively (p=0.192, Paired t-test). Sham operated animals showed no elevation of the IOP 7 days postoperatively. When the ratio between consensual and direct PLR (PLR(ratio)=consensual/direct PLR; pupil of unoperated eye recorded) was examined in rats which developed elevation of the IOP, preoperative values were 92.2+/-4% (mean+/-SEM), 1 week postoperatively 65+/-4% (significantly different from preoperative values, p<0.05 Repeated Measures ANOVA with Dunnett's Multiple Comparison test, n=5), 4 weeks postoperatively 60.6+/-3.2% (p<0.01, n=5). By 8 weeks postoperatively, pupil responses had essentially recovered 75.4+/-6.9% (p>0.05, n=5). Rats whose IOP values did not rise after surgery and sham operated rats did not develop pupil deficits 4 weeks postoperatively. Rats with elevated IOP displayed a significant decrease in ERG amplitudes in operated eyes at 4 weeks (a-wave(operated)/a-wave(control) (a-wave ratio)=42+/-14% (mean+/-SEM); b-wave(operated)/b-wave(control) (b-wave ratio)=43+/-16%) but not at 8 weeks postoperatively (a-wave ratio=88+/-8.4%; b-wave ratio=82.9+/-9%). Sham operated and rats whose IOP values remained non-elevated after surgery did not develop ERG deficits 4 weeks after surgery. Histological analysis did not reveal any damage in the eyes of animals with elevated intraocular ocular pressure with the exception of one rat, which still had ERG and pupil deficits at the end of experiment. CONCLUSIONS: Development of ERG and PLR deficits are proportional to the elevation of the IOP in the rat model of chronic ocular hypertension. Functional monitoring of the ERG and PLR are useful objective techniques for the detection of retina and optic nerve deficits.

Animals↗

Pupil light reflex in normal and diseased eyes: diagnosis of visual dysfunction using waveform partitioning.

OBJECTIVE: To evaluate changes in pupil size (corresponding to neuronal firing) within different time windows of the pupil light reflex in patients and normal subjects to understand which segments of the pupil waveform are best able to differentiate normal from abnormal subjects. DESIGN: Comparative, observational case series. PARTICIPANTS: Forty-nine normal subjects and 25 patients with known unilateral or asymmetric visual field damage were tested. METHODS: A dual-channel infrared pupillograph was used to simultaneously record the right and left pupil diameters at a rate of 60 Hz. Each eye was stimulated alternately (30 degrees full-field, 200 milliseconds duration every 3 seconds) over 10 different stimulus intensities. The recorded waveform of the pupil light reflex was subdivided into six time windows based on landmarks corresponding to contraction onset, maximum contraction velocity, peak contraction, and maximum dilation velocity to assess which portion was most affected by disease. MAIN OUTCOME MEASURES: The linear correlation between pupil contractions elicited by right versus left full-field stimulation at different light intensities provided diagnostic parameters (slope, intercept, and correlation coefficient R(2)) that were useful for differentiating normal subjects from patients and for categorizing disease. Sensitivity and specificity of the time windows were evaluated with receiver-operator curve analysis. RESULTS: The diagnosis of asymmetric disease was greatest at time windows that included pupil contraction but not dilation. When the contraction phase was subdivided into an early phase and into a late phase, the late phase was the most diagnostic compared with the entire phase of contraction amplitude (onset to peak contraction). CONCLUSIONS: By use of a range of light intensity, the change in pupil size measured between the time at which maximum contraction velocity occurs and the time to peak contraction provided the best response parameter for objective diagnosis of asymmetric disease of the anterior visual pathway. The waveform of the pupil light reflex may be an expression of the firing of retinal ganglion cells. Therefore, understanding which segment of the pupil light reflex provides maximal diagnostic power may give insight into how disease affects the pattern of neuronal firing rate.

Diagnostic Techniques, Ophthalmological↗

Characterization of the pupil light reflex, electroretinogram and tonometric parameters in healthy mouse eyes.

PURPOSE: To characterize the pupil light reflex (PLR), electroretinographic (ERG) and tonometric parameters which might be of importance for the in vivo characterization of mouse models of chronic ocular hypertension. METHODS: C57/BL6 mice were used for experiments. The PLR was evaluated with a computerized pupillometer (n = 14), ERGs were recorded simultaneously from both eyes (n = 23) and IOP was measured with a modified Goldmann tonometer (n = 23). RESULTS: The analysis of the PLR parameters confirmed the consensual PLR did not have significantly different amplitude (p > 0.1) and latency time (p > 0.1) compared to the direct PLR. However, PLR velocity (p = 0.004) was significantly smaller in the consensual PLR. Electroretinography revealed a-wave amplitude of 168.3 +/- 9.6 microV with latency of 27.5 +/- 0.6 ms and b-wave 403 +/- 28.8 microV with latency of 22.7 +/- 0.6 ms. The flicker ERG recording revealed amplitudes of 20.6 +/- 2.4 microV. Tonometry experiments revealed that modified Goldmann tonometer measurements correlated well with invasive manometry (r(2) = 0.89). The mean IOP of the mouse was 15.3 +/- 0.6 mmHg. CONCLUSIONS: Consensual PLR in mice is relatively slower than the direct PLR, but retains the same degree of constriction comparing to the direct PLR. A modified Goldmann tonometer seems to be a reliable non-invasive tool for IOP measurements in mice.

Animals↗

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 degrees 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.

Adult↗

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 PLR(ratio)s (indirect/direct PLR) were 76.7 +/- 2.6 (mean +/- SEM). Twenty-four hours after surgery the PLR(ratio) 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 < 0.01, repeated-measures ANOVA). Forty-two days after surgery, the PLR(ratio) 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 microV, injured eyes: 3.4 +/- 1.7 microV). 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.

Acute Disease↗

Laser-induced mouse model of chronic ocular hypertension.

PURPOSE: To develop an inducible mouse model of glaucoma. METHODS: An obstruction of aqueous humor outflow in adult C57BL6/J mice was induced by combined injection of indocyanine green (ICG) dye into the anterior chamber and diode laser treatment. To evaluate intraocular pressure (IOP), tonometry was performed with a modified Goldmann tonometer. The function of the retina was evaluated with electroretinography (ERG). RESULTS: IOP was significantly elevated in surgical eyes compared with control eyes: before surgery, 15.2 +/- 0.6 mm Hg; 10 days after surgery, 33.6 +/- 1.5 mm Hg (P < 0.001); and 30 days after surgery, 27.4 +/- 1.2 mm Hg (P < 0.001). However, 60 days after surgery, IOP in the surgical eyes decreased to 19.5 +/- 0.9 mm Hg and was not significantly different compared with control eyes (control, 17.3 +/- 0.7 mm Hg; P = 0.053). ERG amplitudes, expressed as a ratio (surgical/control), were decreased in surgical eyes. The amplitudes for b-wave were: before surgery, 107.6% +/- 4.6%; 28 days after surgery, 61% +/- 4% (P < 0.001); and 56 days after surgery, 62% +/- 5.6% (P < 0.001). Oscillatory potentials were the most dramatically affected: before surgery, 108.6% +/- 6.7%; 28 days after surgery, 57.5% +/- 5% (P < 0.01); and 56 days after surgery, 57% +/- 8.5% (P < 0.001). Amplitudes of the a-waves had relatively smaller but still significant deficits: before surgery, 105.8% +/- 6.9%; 28 days after surgery, 72.2% +/- 5.4% (P < 0.01); and 56 days after surgery, 79.8% +/- 11.0% (P < 0.01). Histologic analysis of the surgical eyes revealed development of anterior synechia, loss of retinal ganglion cells (RGCs), and thinning of all retinal layers. Electron microscopy of optic nerve cross sections revealed swelling and degeneration of the large diameter axons and gliosis. CONCLUSIONS: Diode laser treatment of ICG saturated episcleral veins causes a chronic elevation of IOP and sustained ERG deficits.

Animals↗