Lori M. Ventura

Pattern electroretinogram in glaucoma

Purpose of review Several studies have shown that the pattern electroretinogram, a direct, objective method of measuring retinal ganglion cell function, is altered early in ocular hypertension and glaucoma. Renewed interest in the pattern electroretinogram for early detection of pre-perimetric glaucoma has been sparked by noninvasive and reproducible methods of recording using skin electrodes. Recent findings With the noninvasive pattern electroretinogram, response abnormalities have been detected in up to 50% of glaucoma suspects with normal standard perimetry. In early glaucoma (with either normal or high intraocular pressure), a reduction of intraocular pressure has sometimes yielded improvement in pattern electroretinogram amplitude. A prolonged steady-state stimulus presentation reduces the pattern electroretinogram amplitude and increases optic nerve blood flow in normal subjects, suggesting that sustained activity of retinal ganglion cells is physiologically associated with autoregulatory changes of the neural-vascular system. It is unknown whether this autoregulation is altered in glaucoma. The multifocal pattern electroretinogram does not seem to have an advantage over the pattern electroretinogram in the early detection of glaucoma. The photopic negative response of the diffuse flash electroretinogram has shown changes in glaucoma, but may not be able to detect retinal dysfunction in normal tension glaucoma. Summary The pattern electroretinogram is a noninvasive, direct, objective method that may be useful to clinicians in detecting early retinal ganglion cell dysfunction in glaucoma suspects. The pattern electroretinogram may also optimize treatment strategies based on improvement of retinal ganglion cell function.

Progressive Loss of Retinal Ganglion Cell Function Precedes Structural Loss by Several Years in Glaucoma Suspects

PURPOSE We determined the time lag between loss of retinal ganglion cell function and retinal nerve fiber layer (RNFL) thickness. METHODS Glaucoma suspects were followed for at least four years. Patients underwent pattern electroretinography (PERG), optical coherence tomography (OCT) of the RNFL, and standard automated perimetry testing at 6-month intervals. Comparisons were made between changes in all testing modalities. To compare PERG and OCT measurements on a normalized scale, we calculated the dynamic range of PERG amplitude and RNFL thickness. The time lag between function and structure was defined as the difference in time-to-criterion loss between PERG amplitude and RNFL thickness. RESULTS For PERG (P < 0.001) and RNFL (P = 0.030), there was a statistically significant difference between the slopes corresponding to the lowest baseline PERG amplitude stratum (≤50%) and the reference stratum (>90%). Post hoc comparisons demonstrated highly significant differences between RNFL thicknesses of eyes in the stratum with most severely affected PERG (≤50%) and the two strata with least affected PERG (>70%). Estimates suggested that the PERG amplitude takes 1.9 to 2.5 years to lose 10% of its initial amplitude, whereas the RNFL thickness takes 9.9 to 10.4 years to lose 10% of its initial thickness. Thus, the time lag between PERG amplitude and RNFL thickness to lose 10% of their initial values is on the order of 8 years. CONCLUSIONS In patients who are glaucoma suspects, PERG signal anticipates an equivalent loss of OCT signal by several years.

Viability of herpes simplex virus type 1 on the applanation tonometer.

We performed several experiments to define possible factors that influence the viability of herpes simplex virus type 1 on the applanation tonometer. Infectious virus could be detected on experimentally inoculated tonometer heads for up to two hours during natural drying. If tonometers were kept moist the virus could be detected more than eight hours later. Several ophthalmic solutions, including topical anesthetics, dilating agents, and a fluorescein solution, showed only minimal antiviral activities. Wiping of virus-infected tonometer heads with a dry tissue was ineffective and allowed residual infectious virus to remain. However, no infectious virus could be detected on infected tonometer heads that had been swabbed with 70% isopropyl alcohol. Our results raised concerns regarding effective disinfection of tonometers after eye examinations. We concluded that the applanation tonometer should be swabbed routinely with alcohol after each patient examination to ensure complete virus inactivation and to prevent accidental transmission of virus in the clinical setting.

Pattern electroretinogram and glaucoma.

Purpose of review Several studies have shown that the pattern electroretinogram, a direct, objective method of measuring retinal ganglion cell function, is altered early in ocular hypertension and glaucoma. Renewed interest in the pattern electroretinogram for early detection of pre-perimetric glaucoma has been sparked by noninvasive and reproducible methods of recording using skin electrodes.

Retinal Ganglion Cell Functional Plasticity and Optic Neuropathy: A Comprehensive Model

Abstract: The clinical management of glaucoma and optic neuropathies has traditionally focused on stages of the diseases at which there are congruent losses of visual function and optic nerve tissue. Increasing clinical and experimental evidence suggests that the electrical activity of retinal ganglion cells, as measured by pattern electroretinogram (PERG), may be altered long before measurable changes in the thickness of the retinal nerve fiber layer. In addition, PERG alterations in early glaucoma may be either reversed by lowering the intraocular pressure or induced with head-down body posture. Here we apply the well-known concept of neural plasticity to model the reversible/inducible changes of retinal ganglion cell electrical activity during a critical period of dysfunction preceding death. Identification and characterization of this stage of modifiable retinal ganglion cell function represents both a rationale and a target for treatment to change the natural history of the disease.

Physiologic significance of steady-state pattern electroretinogram losses in glaucoma: clues from simulation of abnormalities in normal subjects.

PurposeTo better understand pathophysiologic mechanisms underlying pattern electroretinogram (PERG) losses in glaucoma by simulating either retinal ganglion cell (RGC) dysfunction or RGC loss in normal subjects. Materials and MethodsThe steady-state PERG has been recorded in 10 normal subjects (mean age: 31±8 y) according to the PERGLA paradigm by means of skin electrodes in response to horizontal gratings (1.7 cycles/degree, 99% contrast, 40 cd/m2 mean luminance, circular field size 25 degree diameter) alternating 16.28 times/seconds. Simulated RGC dysfunction has been obtained by reducing either contrast and mean luminance or blurring the visual stimulus. Simulated RGC loss has been obtained by reducing stimulus area. Outcome measures were PERG amplitude and phase obtained by discrete Fourier transform of PERG waveforms. ResultsProgressive PERG amplitude reductions spanning the entire dynamic range of PERG response could be obtained by progressively reducing stimulus contrast and luminance, blurring the stimulus, and reducing stimulus area. The same variations in stimulus conditions caused phase changes of disparate sign and magnitude. Phase advanced (latency shortened) by reducing stimulus contrast or blurring the stimulus; phase lagged (latency increased) by reducing stimulus luminance; phase remained constant by reducing stimulus area. ConclusionsPERG amplitude and phase are essentially uncoupled, implying that these measures reflect distinct aspects of RGC activity. On the basis of our results and known PERG physiology, we propose a model in which both RGC dendrites and RGC axons contribute to the PERG signal. PERG delays may represent an indication of synaptic dysfunction that is potentially reversible.

Head-down posture induces PERG alterations in early glaucoma

Purpose:To probe susceptibility of retinal ganglion cells (RGC) to physiological stressors associated with moderate head-down body tilt in patients with suspicion of glaucoma or early manifest glaucoma (EMG). Methods:One hundred nine subjects with best corrected visual acuity (BCVA) ≥20/20 and no disease other than glaucoma [glaucoma suspects (GS)=79, EMG=14, normal controls (NC)=16 and comparable age range were tested. Noncontact intraocular pressure (IOP), pattern electroretinogram (PERG), and brachial blood pressure/heart rate measurements were performed in 3 consecutive conditions (∼0038 min apart): seated (baseline), −10-degree whole body head-down tilt (HDT), and seated again (recovery). PERG amplitude and latency, IOP, and systolic/diastolic blood pressures, heart rate, calculated mean central retinal artery pressure, ocular perfusion pressure, and systolic/diastolic perfusion pressures were evaluated. Results:During HDT, IOP significantly (P<0.001) increased in all groups approximately to the same extent (approximately 20%). PERG amplitude did not change in NC but decreased significantly (P<0.001) in patients (GS, −25%, EMG −23%). PERG phase become delayed in NC (−1.6%, P=0.04) but more so in patients (GS, −2.7%, P<0.001; EMG, −6.0%, P<0.001). The proportion of patients with PERG alterations significantly (P<0.05) exceeding those occurring in age-adjusted and baseline-adjusted NC were, GS: amplitude 20%, phase 15%; EMG: amplitude 14%, phase 50%. All measures recovered baseline values after HDT. Conclusions:Moderate HDT induces temporary worsening of RGC function in a subpopulation of GS and EMG patients. This noninvasive protocol may help disclose abnormal susceptibility of RGCs in a subset of the patients at risk of glaucoma.

Progressive loss of retinal ganglion cell function is hindered with IOP-lowering treatment in early glaucoma

PURPOSE To investigate progressive changes of retinal ganglion cell (RGC) function in glaucoma suspects before and after IOP-lowering treatment. METHODS The authors retrospectively analyzed pattern electroretinograms (PERG) recorded twice a year in 32 glaucoma suspects over at least 6 years. Fifteen patients (28 eyes in the study group) received IOP-lowering treatment at intermediate points during the follow-up, thereby generating a break point between the untreated period and the treated period. Seventeen patients (31 eyes in the control group) were not treated; a break point in the follow-up period was randomly assigned. To assess the effect of treatment, linear regression slopes of PERG amplitude were calculated for periods before and after the break point, and compared both within and between groups. Linear mixed models applied to raw PERG amplitudes recorded over the entire follow-up period were also calculated. RESULTS Before the break point, slopes had a similar negative trend in both groups, whereas after the break point the slope became shallower in the treated group (P = 0.002). The linear mixed model revealed an interaction between groups, period relative to break point, and segment duration (P = 0.001). Both analyses agreed that after the break point, the rate of PERG amplitude decline slowed in treated eyes by 0.013-0.019 μV/year compared with the untreated eyes. Mean IOPs measured before and after break point were similar in control eyes (14.8 ± 3.20 vs. 14.8 ± 3.14 mm Hg) but different in treated eyes (16.84 ± 3.96 vs. 14.8 ± 3.24 mm Hg; P < 0.001). CONCLUSIONS Progressive loss of RGC function in early glaucoma may be alleviated after IOP lowering, as measured by PERG.

Pattern electroretinogram progression in glaucoma suspects

Purpose:To prospectively monitor progressive changes of retinal ganglion cell function in early glaucoma using the pattern electroretinogram (PERG). Methods:Fifty-nine patients enrolled as glaucoma suspects were observed untreated over an average of 5.7±1.4 years, during which they were tested with PERG (PERGLA paradigm) and standard automated perimetry (SAP) 2 times per year. PERG amplitude and phase were normalized for physiological age-related changes, and linear regressions fitted to the data to calculate progression slopes (signal), slope SE (noise), and corresponding signal-to-noise ratios (SNR=slope÷SE). Linear regressions were also used to fit SAP global indices mean deviation (MD) and pattern standard deviation (PSD). Results:On average, progression slopes of PERG amplitude/phase were skewed toward negative values, their mean being significantly (P<0.01) different from zero. In contrast, mean slopes of SAP-MD and PSD were not significantly different from zero. SNRs were higher for PERG than SAP (P<0.01). A substantial number of eyes displayed significant (P<0.05) progression of PERG amplitude (15% to 20%) or PERG phase (16% to 25%). Fewer eyes displayed significant progression of SAP-MD (0% to 2%) or SAP-PSD (4% to 8%). Conclusions:The PERG displayed clear longitudinal loss of signal (diminished amplitude, phase delay, or both) in a substantial number of eyes of patients, indicating progressive deterioration of retinal ganglion cell function. Progression of SAP global indices MD and PSD was found in a relatively smaller number of eyes. It remains to be established whether PERG progression has predictive value for developing visual dysfunction.

Reversible dysfunction of retinal ganglion cells in non-secreting pituitary tumors

A large cohort of patients participated in a longitudinal study of early glaucoma progression. During follow up, six eyes of three patients displayed a relatively rapid deterioration of pattern electroretinogram (PERG) signal compared to changes in visual acuity, IOP, Standard Automated Perimetry, and Retinal Nerve Fiber Layer thickness measured by OCT. This deterioration prompted further testing including magnetic resonance imaging (MRI), which revealed pituitary tumors in all three patients, two of which were abutting but not compressing the chiasm. Following tumor resection, the PERG signal gradually recovered to baseline values in all six eyes. Results indicate that pituitary tumors may cause retrograde dysfunction of retinal ganglion cells (RGC) even in the absence of visible mechanical compression of the visual pathway, and such dysfunction may be reversed by tumor reduction. The results suggest that PERG is a useful tool in the early diagnosis and management of patients with chiasmal mass lesions.