Abstract: PURPOSE: To assess macular structure and function by optical coherence tomography (OCT) and focal electroretinogram (FERG) before and after intravitreal triamcinolone acetonide (IVTA) administration for cystoid macular edema (CME) in a patient with retinitis pigmentosa (RP). METHODS: A 33-year-old man with RP and refractory bilateral macular edema was treated with IVTA in his left eye and evaluated with visual acuity, OCT, and FERG for 6 months. RESULTS. Compared to the fellow eye, after IVTA mean retinal thickness significantly decreased, while FERG amplitude and phase did not show significant changes at the end of follow-up. Visual acuity showed a significant tendency to improve. CONCLUSIONS: In this case report, IVTA improved macular anatomy and visual acuity; this result, however, was not associated with a similar electrophysiologic response.
Abstract: PURPOSE: To assess short-term changes in macular function after transpupillary thermotherapy (TTT) in patients with occult subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD), using focal electroretinography (FERG). METHODS: Twenty-five patients with occult subfoveal CNV due to AMD were treated with TTT delivered using an infrared (810 nm) diode laser (spot size 3.0 mm, laser power 400-600 mW, duration 60 seconds). All patients were clinically evaluated before, 1 and 6 weeks after treatment. Snellen visual acuity (VA) was measured at each visit. Fluorescein angiography (FA) was performed at baseline and 6 weeks after TTT. Focal ERGs were recorded in all patients immediately before and 1 week after TTT in response to an 18-degree diameter, 41 Hz flickering spot (630 nm) centred on the fovea, presented on a steady background in Maxwellian view. A subgroup of 12 patients was also re-tested by FERG at 6-weeks post-TTT. RESULTS: No significant changes in mean FERG amplitude and phase were observed across the different recording sessions before and after TTT. One week after TTT, four patients had significant (> 2 SD from baseline variability) increases in FERG amplitude and/or phase advances, one had a decrease in amplitude and four had phase delays, compared to baseline. The remaining 15 patients had stable FERGs. Six weeks after TTT, four patients had significant increases in FERG amplitude and/or phase advances, four had decreases in amplitude and/or phase delays, and four had stable FERGs, compared to baseline. Improvement in FERG parameters after TTT was always associated with an improvement in VA and a decrease in exudation. Patients with post-TTT FERG deterioration had stable or deteriorated clinical pictures. At either 1 or 6 weeks post-TTT, the FERG amplitude increase was inversely correlated (p < 0.05) with the baseline FERG amplitude and VA. CONCLUSIONS: Three major conclusions can be drawn: in a short-term follow-up, TTT was not found to be associated with significant changes in macular function; FERG improvement was associated with VA improvement, and the increase in FERG amplitude was greatest in patients with the worst baseline acuity.
Abstract: Retinitis pigmentosa is the most common form of retinal degeneration and is heterogeneous both clinically and genetically. The autosomal dominant forms (ADRP) can be caused by mutations in 12 different genes. This report describes the first simultaneous mutation analysis of all the known ADRP genes in the same population, represented by 43 Italian families. This analysis allowed the identification of causative mutations in 12 of the families (28% of the total). Seven different mutations were identified, two of which are novel (458delC and 6901C-->T (P2301S), in the CRX and PRPF8 genes, respectively). Several novel polymorphisms leading to amino acid changes in the FSCN2, NRL, IMPDH1, and RP1 genes were also identified. Analysis of gene prevalences indicates that the relative involvement of the RHO and the RDS genes in the pathogenesis of ADRP is less in Italy than in US and UK populations. As causative mutations were not found in over 70% of the families analysed, this study suggests the presence of further novel genes or sequence elements involved in the pathogenesis of ADRP.
Abstract: The retina and optic nerve are both optically accessible parts of the central nervous system. They represent, therefore, highly valuable tissues for studies of the intrinsic physiological mechanism postulated more than 100 years ago by Roy and Sherrington, by which neural activity is coupled to blood flow and metabolism. This article describes a series of animal and human studies that explored the changes in hemodynamics and oxygenation in the retina and optic nerve in response to increased neural activity, as well as the mechanisms underlying these changes. It starts with a brief review of techniques used to assess changes in neural activity, hemodynamics, metabolism and tissue concentration of various potential mediators and modulators of the coupling. We then review: (a) the characteristics of the flicker-induced hemodynamical response in different regions of the eye, starting with the optic nerve, the region predominantly studied; (b) the effect of varying the stimulus parameters, such as modulation depth, frequency, luminance, color ratio, area of stimulation, site of measurement and others, on this response; (c) data on activity-induced intrinsic reflectance and functional magnetic resonance imaging signals from the optic nerve and retina. The data undeniably demonstrate that visual stimulation is a powerful modulator of retinal and optic nerve blood flow. Exploring the relationship between vasoactivity and metabolic changes on one side and corresponding neural activity changes on the other confirms the existence of a neurovascular/neurometabolic coupling in the neural tissue of the eye fundus and reveals that the mechanism underlying this coupling is complex and multi-factorial. The importance of fully exploiting the potential of the activity-induced vascular changes in the assessment of the pathophysiology of ocular diseases motivated studies aimed at identifying potential mediators and modulators of the functional hyperemia, as well as conditions susceptible to alter this physiological response. Altered hemodynamical responses to flicker were indeed observed during a number of physiological and pharmacological interventions and in a number of clinical conditions, such as essential systemic hypertension, diabetes, ocular hypertension and early open-angle glaucoma. The article concludes with a discussion of key questions that remain to be elucidated to increase our understanding of the physiology of ocular functional hyperemia and establish the importance of assessing the neurovascular coupling in the diagnosis and management of optic nerve and retinal diseases.
Abstract: OBJECTIVE: To evaluate long-term anatomical and functional outcomes of a modified osteo-odonto-keratoprosthesis (OOKP) technique for treatment of corneal blindness from various etiologies. METHODS: Two-hundred three patients (224 eyes) underwent modified OOKP surgery between 1973 and 1999. Of the original cohort, 181 patients (98 men and 83 women; mean [SD], age 54.3 [15] years) in whom a standardized 2-step surgical procedure was performed were included in the study. Preoperative diagnoses were dry eye (n = 70) due to ocular pemphigoid (n = 39), Sjögren syndrome (n = 11), trachoma (n = 8), Lyell syndrome (n = 6), Stevens-Johnson syndrome (n = 4), and graft-vs-host disease (n = 1) and congenital lid coloboma (n = 1), severe corneal burns (n = 68), bullous keratopathy (n = 13), keratitis sequelae (n = 15), and bullous keratopathy secondary to antiglaucoma surgery (n = 15). Several innovations were made to the original Strampelli technique. Median follow-up duration was 12 years (range, 1-25 years). RESULTS: Anatomical complications leading to OOKP loss were found in 11 (6.07%) of 181 patients. Survival analysis estimated that 18 years after surgery, the probability of retaining an intact OOKP was 85% (95% confidence interval, 79.3%-90.7%). Pooling patient groups, mean (SD) best postoperative visual acuity was 0.76 (0.34). Mean (SD) final acuity at the end of follow-up declined slightly (0.69 [0.39]) but significantly (P<.01). In individual diagnostic groups, mean acuity decline reached statistical significance (P<.05) only in the pemphigoid (1 line), trachoma (1 line), and bullous keratopathy secondary to antiglaucoma surgery (2 lines) groups. Survival analysis estimated that 18 years after surgery, the probability of retaining best postoperative visual acuity (within 2 lines) was mean (SD) 55.5% (12.9%). CONCLUSION: Modified OOKP surgery for corneal blindness of different etiologies may provide, in the long-term, anatomically stable corneal prosthesis as well as an effective, rehabilitating recovery in visual acuity.
Abstract: PURPOSE: To evaluate retinal thickness at the posterior pole of the fundus in ocular hypertension (OHT) and open-angle glaucoma (OAG), and to correlate morphometric findings with visual sensitivity as determined by automated perimetry. METHODS: One randomly selected eye from 41 patients with clinical diagnosis of OHT (n = 25) or early to moderate OAG (n = 16) and 16 age-matched normal controls was examined. Retinal thickness was measured by Retinal Thickness Analyzer (RTA), acquiring 5 pre-defined scans covering the central 20 degrees of the fundus. RTA average thickness and thickness profile data, including hemispheric asymmetries calculated as relative (superior/inferior and nasal/temporal) or absolute (vertical and horizontal, ie, independent of which hemisphere was thinner) parameters, were calculated. For each eye, white-on-white Humphrey 30-2 visual field results were analyzed, in addition to standard global indices, by quantifying perimetric sensitivities for regions of the posterior pole corresponding to those sampled by the RTA. RESULTS: On average, central retinal thickness was reduced (P < 0.05) in OAG compared with OHT or normal control eyes. Vertical hemispheric absolute thickness asymmetry was increased (P < or = 0.01) in OAG eyes compared with the other groups. Horizontal hemispheric absolute thickness asymmetry was increased (P < 0.01) in both OHT and OAG eyes, compared with control eyes. At least one of the RTA parameters was altered in 13 of 25 OHT (52%) and 12 of 16 OAG eyes (75%), most frequently involving thickness asymmetries. In OAG, but not OHT eyes, superior/inferior asymmetry was positively (r = 0.69, P < 0.01) correlated with the corresponding asymmetry in perimetric sensitivity. CONCLUSIONS: The RTA can reveal increased hemispheric thickness asymmetries in both OHT and OAG eyes. In OAG eyes thickness asymmetries are associated with corresponding perimetric asymmetries. The findings in OHT eyes suggest that localized anatomic and functional damage to inner retina may not develop in parallel early in the disease process.
Abstract: PURPOSE: To evaluate regional cone system function after uncomplicated retinal detachment (RD) surgery, by recording focal electroretinograms (FERGs) from the central and paracentral regions of the posterior pole. METHODS: FERGs in response to either a central (eccentricity: 0-2.25 deg) or a paracentral annular (2.25-9 deg) uniform field, presented on a light adapting background and sinusoidally flickered at 41 Hz (95% modulation depth, 93 cd/m(2) mean luminance) were recorded from 16 eyes (16 patients) 2 weeks to 420 months following uncomplicated RD surgery (encircling procedure with or without scleral buckling). Pre-operatively, 10 out of 16 eyes had a macular RD. Mean time elapsed from onset of symptoms to surgery was 20 days (range: 5-90 days). Post-operatively, visual acuity ranged 0.1 to 1.0. Eight age-matched normal subjects served as controls. Amplitude and phase of the FERG fundamental harmonic were measured. RESULTS: Compared to control eyes, affected eyes' central and paracentral FERGs were on average reduced in amplitude (by 40% and 28%, respectively, p<0.01) and delayed in phase (by 70 and 100 degrees, respectively, p<0.01). Eyes with a macular RD did not differ in FERG amplitude or phase from eyes that had a peripheral RD. In individual affected eyes, central, but not paracentral FERG amplitudes were negatively correlated (p=0.05) with time elapsed from onset of symptoms to surgery. CONCLUSIONS: Central and paracentral cone system dysfunction may be detected even at lengthy time intervals from retinal reattachment, independent of the presence of a pre-operative macular RD. The extent of central loss appears to be inversely related to RD duration, in agreement with previous reflectometric findings on foveal cone photopigment density [Liem et al., 1994; Ophthalmology 10: 1945-51].
Abstract: Near-infrared laser Doppler flowmetry was applied in 15 normal volunteers to record the time course and magnitude of changes in the velocity (Vel), volume (Vol) and flow (F) of blood and tissue reflectance (R) at the optic disk in response to 40 and 50 s of increased retinal neural activity. This activity was evoked by diffuse luminance flicker of the retinal posterior pole. After 20 s of flicker, the group averages of Vel, Vol, and F were significantly higher than at baseline (pre-flicker) by 12, 24 and 38%. Time constants of the increases in Vel, Vol, and F were 3.4, 12.7 and 9.1 s, respectively. The group average change in R of 1% was not significant. However, in one subject, 15 recordings from the same site of the optic disk showed a significant increase in R of 8%, with a time course similar to that of Vol. Our findings show that, in the human optic nerve, a white matter tissue, the temporal dynamics and magnitude of the response of blood flow to an increase in retinal neural activity are similar to those reported for brain gray matter. Furthermore, although the R-response could be due, in part, to changes in blood volume, other factors, such as activity-evoked tissue scattering changes, may also affect this response.
Abstract: Considerable progress has been made in the understanding and management of degenerative diseases of the retina. The dietetic intervention has been favourably proposed in the most common forms of retinitis pigmentosa, a condition potentially leading to blindness. Vitamin A has been shown to be effective in delaying progression of the disease. In these patients such treatment is the only possible therapy, to date, and a lifetime generous supplementation of retinol is advisable, together with a vitamin A-rich diet and/or a dietary supplement (e.g. carrot flour) or pharmacologic supplement of vitamin A. Supply of vitamin A in doses up to 25000 IU (7500 igr/day), even for several years, has so far proved safe from risk of occurrence of liver disease. A possible effect on hypercholesterolemia related to a very prolonged treatment in predisposed individuals can be avoided by using a special diet, particularly enriched with beta-carotene. Guidelines for preparing a diet, specially formulated to provide an elevated weekly supply of vitamin and/or its precursor (equal to 15000 IU or 5000 microg of RE, retinol equivalent) and to control possible risk factors related to dietetic manipulation (supply of fat lower than 30% of total calories, variable levels of cholesterol and polyunsaturated fatty acids n-3, n-6) are presented. As long as resolutive therapy is lacking, dietetic intervention plays a primary role, although underestimated, in the management of the patients suffering from retinitis pigmentosa. The diet is specifically characterized by presence of food with a high content of carotenoids, substances with a favourable and additive effect.
Abstract: OBJECTIVE: To evaluate a fast technique of visual evoked potentials (VEPs) recording, in response to steady-state luminance stimuli (SS-LVEPs), for functional assessment and follow-up of childhood optic gliomas (OGs). METHODS: Eighteen OG patients (age range: 3.5-18 years), with different degrees of optic pathway damage severity, were examined. Sixteen age-matched normal subjects served as controls. Ten of the 18 OG patients were re-tested 1-3 months after the first examination. SS-LVEPs were elicited by a sinusoidally-modulated flickering (8 Hz) uniform field, generated by a light emitting diode (LED)-array and presented monocularly in a mini-ganzfeld. Amplitude and phase of the Fourier-analyzed response fundamental (1F) and second harmonic (2F) were measured. The full VEP protocol had a median duration of 6 min (range: 4-12). RESULTS: When compared to normal control values, median 1F and 2F SS-LVEP amplitudes of OG patients were reduced (P<0.01), with a borderline increase in 2F phase lag (P<0.05). In 11 OG patients with asymmetric optic pathway damage in between-eye comparisons, median 1F amplitude losses were greater (P<0.01) in fellow eyes with more severe damage. No significant interocular difference was observed in control subjects. Median test-retest changes of 1F and 2F component were <20% and 30 degrees for amplitude and phase, respectively. In individual OG patients, 1F and 2F amplitudes were positively correlated (P<0.01) with visual acuity. 1F amplitude losses were correlated (P=0.01) with the severity of optic disc atrophy. Considering both 1F and 2F abnormalities, diagnostic sensitivity of SS-LVEP in detecting OG-induced optic pathways damage was 83.3%. CONCLUSIONS: The present findings support the use of this technique, as an alternative to pattern VEPs, for functional assessment and follow-up of OG in uncooperative children.
Abstract: PURPOSE: To determine in patients with ocular hypertension (OHT) or early glaucoma (EOAG) the change in blood flow measured at the neuroretinal rim of the optic disc in response to a 15-Hz diffuse green luminance flicker, a stimulus that activates predominantly the ganglion cell magnocellular pathway. METHODS: Thirteen patients with EOAG, 29 with OHT, and 16 age-matched control subjects, all with excellent fixation, were examined. Blood flow (F(onh)) at the neuroretinal rim of the optic disc was continuously monitored by laser Doppler flowmetry before and during exposure to a 15-Hz, 30 degrees field green luminance flicker. The response of F(onh) to this stimulus (RF(onh)) was expressed as percentage change in F(onh) between baseline and the last 20 seconds of flicker. Two to three temporal sites of the disc were tested, and the highest RF(onh) was considered for further analysis. RF(onh) results in patients were correlated with morphologic (cup-to-disc area ratio, cup shape neuroretinal rim area) and functional (perimetric mean deviation and pattern electroretinogram amplitude) clinical parameters. RESULTS: In the patients with OHT or EOAG, F(onh) and RF(onh) were both reduced compared with their respective values in the control group. Both quantities decreased significantly with neuroretinal rim area when the patients' data were pooled. No significant correlation was found between F(onh) or RF(onh) and the other morphometric and functional parameters. The group-averaged time course of RF(onh) was not significantly different from that in the normal subjects. CONCLUSIONS: Luminance flicker-evoked RF(onh) is abnormally reduced in patients with OHT or EOAG, indicating an impairment of neurally mediated vasoactivity. The data suggest that PERG-derived neural activity and flicker-evoked RF(onh) can be independently altered early in the disease process.
Abstract: To investigate the effects of quinine on the electroretinograms (ERGs) of children with cerebral malaria (CM), we recruited subjects during a single malaria season in Blantyre, Malawi. Seventy ERG investigations were performed, on 34 children with CM. Time recorded from completion of the most recent quinine infusion was termed "quinine elapsed time" (QET). In a subgroup of 16 children, whole-blood quinine concentrations were estimated in a sample of capillary blood, for validation. A significant positive association was found between QET and both maximal-response A-wave amplitude (MRAWA; P=.03) and cone A-wave amplitude (P=.04). Longitudinal analysis demonstrated a significant trend of increasing MRAWA with increasing QET (P=.03). Parenteral quinine administered in therapeutic doses to a pediatric population appears to cause a transient depression in photoreceptor function. No evidence of ocular quinine toxicity was found at the therapeutic doses used.
Abstract: PURPOSE: To use focal electroretinography to evaluate changes in retinal function during transpupillary thermotherapy (TTT) for neovascular age-related macular degeneration (ARMD). METHODS: Sixteen eyes of 16 patients with ARMD with occult choroidal neovascularization (CNV) were studied. A 630-nm photocoagulator aiming beam was modified for use as a 41-Hz square-wave focal electroretinogram (fERG) stimulus. The stimulus was presented on a light-adapting background by a Goldmann-type lens (visual angle, 18 degrees; mean luminance, 50 cd/m(2)). fERGs were continuously monitored before, during, and after TTT for occult CNV. The amplitude and phase of the fERG's fundamental harmonic were measured. RESULTS: No suprathreshold or adverse clinical events occurred during the course of the study. fERG amplitude decreased transiently during TTT (23% +/- 9% [SE]; P < 0.05). The decrease in amplitude was greatest 16 to 20 seconds and 32 to 40 seconds after the onset of TTT. It was followed by a recovery to baseline amplitude during TTT (48 to 60 seconds after TTT was begun). Within 60 seconds after TTT was completed, fERG amplitude was within the range of baseline. TTT did not alter the fERG phase. Mean fERG amplitudes and phases recorded 1 week and 1 month after TTT were comparable to mean pretreatment levels. CONCLUSIONS: fERG amplitude decreases transiently during TTT, despite the absence of ophthalmoscopically apparent lesions. Intraoperative amplitude depression may result from an adaptation effect to laser light energy and/or hyperthermia, resulting in desensitization of cone photoreceptors and bipolar cells. Treatment sites are electrophysiologically functional 1 month after TTT. Detailed parametric study of a larger patient group is needed to determine whether fERG testing is potentially useful for monitoring and perhaps for controlling and optimizing TTT for choroidal neovascularization.
Abstract: This is a brief review of data obtained by analyzing the morphology and the physiology of the retinas in rd/rd and normal, wt mice, aged 10-90 days. Second-order neurons of the rd/rd show abnormalities that start with the anomalous development of rod bipolar cells around P10 and culminate with the atrophy of dendrites in cone bipolar cells, mostly evident at P90. Horizontal cells remodel considerably. Cone-mediated ERGs, (recorded between 13 and 16 days of age) have reduced a-wave and b-wave amplitudes and longer b-wave latency and duration. B-wave abnormalities indicate specific postreceptoral dysfunction. Morphological and ERG changes in rd/rd retinas are consistent with substantial inner retinal remodeling associated to photoreceptor degeneration.
Abstract: PURPOSE: To evaluate regional cone dysfunction in retinitis pigmentosa (RP) by recording focal electroretinograms (FERGs) from the central and paracentral retinal regions and to correlate the FERG with perimetric sensitivity losses. METHODS: Twenty-three typical patients with RP (age, 18-65 years; visual acuity, 20/100 to 20/20; kinetic visual field by size II/4e, 20-40 degrees ) and eight age-matched control subjects were evaluated. FERGs were recorded in response to either a central (eccentricity, 0-2.25 degrees ) or a paracentral annular (2.25-9 degrees ) field, presented on a light-adapting background. Fields' luminances (mean: 80 cd/m(2)) were sinusoidally modulated at different temporal frequencies (TFs; 10.3, 14, 21, 32, 41, and 52 Hz). Amplitude and phase of the responses' fundamental harmonic (1F) were measured. Perimetric sensitivity was measured by a visual field perimeter. For each patient, mean sensitivity losses were calculated for both the central (0-2.25 degrees ) and paracentral (2.25-9 degrees ) regions. RESULTS: On average, central and paracentral FERGs of patients with RP were reduced in amplitude (P </= 0.05) compared with control values. Amplitude losses tended to be smaller in the central than the paracentral region and were limited to low-medium TFs (10.3-14 Hz). Paracentral losses were rather invariant with TF. Paracentrally, but not centrally, the FERG phase in patients was delayed on average (P < 0.01), compared with control values. The central FERG phase was delayed only in patients with visual acuities less than 20/40. In individual patients, paracentral 41-Hz amplitude losses were positively correlated with corresponding perimetric losses (r = 0.7, P < 0.005). Both central and paracentral 41-Hz amplitudes displayed high specificity (87.5% and 100%, respectively) with relatively low sensitivity (46.6% and 63.6%, respectively) in predicting perimetric results in corresponding retinal regions. CONCLUSIONS: In RP, central and paracentral FERGs are differently altered as a function of TF, indicating regional differences in the stage and/or pathophysiology of retinal cone dysfunction. FERG abnormalities may predict, to some extent, perimetric results at corresponding retinal regions. The data support the use of the present FERG method to evaluate regional cone dysfunction in different stages of RP.
Abstract: PURPOSE: To evaluate the influence of short-term antioxidant supplementation on retinal function in age-related maculopathy (ARM) patients by recording focal electroretinograms (FERGs). DESIGN: Nonrandomized, comparative clinical trial. PARTICIPANTS: Thirty patients with early ARM and visual acuity >/=20/30, divided into two groups, similar for age and disease severity: antioxidant group (ARM-A, n = 17) and no treatment group (ARM-NT, n = 13). Eight age-matched normal subjects divided into antioxidant (N-A, n = 4) or no treatment (N-NT, n = 4) groups. METHODS: ARM-A patients and N-A patients had oral supplementation of lutein, 15 mg; vitamin E, 20 mg; and nicotinamide, 18 mg, daily for 180 days, whereas ARM-NT patients and N-NT patients had no dietary supplementation during the same period. Eight of the 17 ARM-A patients took supplementation for an additional 180-day period. In all patients and normal subjects, FERG assessment was performed at the study entry (baseline) and after 180 days. Further testing was performed at 360 days for the eight ARM-A patients taking supplements and for one ARM-A patient who had discontinued supplementation after 180 days. FERGs were recorded in response to a 41-Hz sinusoidally modulated uniform field (93.5% modulation depth) presented to the macular region (18 degrees ) on a light-adapting background. In a subgroup of patients (11 ARM-A and 5 ARM-NT), whose responses had suitable signal-to-noise ratios, FERGs were also recorded at different stimulus modulation depths between 8.25% and 93.5%. MAIN OUTCOME AND MEASURES: Amplitude (in micro V) and phase (in degrees) of the FERG fundamental harmonic component. FERG modulation thresholds, estimated from the value of log modulation depth yielding a criterion response. RESULTS: At 180 days, FERGs of ARM-A patients and N-A patients were increased in amplitude (mean change, 0.11 and 0.15 log micro V, respectively, P </= 0.01) compared with baseline values, whereas no significant changes in FERG amplitudes of ARM-NT patients and N-NT patients were found (mean change, -0.004 and -0.023 log micro V, respectively). In all groups no changes in the FERG phase were found. FERG modulation thresholds decreased with respect to baseline values (mean change, -0.36 log units, P < 0.01) in ARM-A patients, whereas no significant change (mean change, 0.07 log units) in ARM-NT patients was seen. At 360 days, FERGs of ARM-A patients taking supplementation were still increased in amplitude with respect to baseline (P < 0.05) but did not differ from those recorded at 180 days. In the patient who had discontinued supplementation, FERG amplitude decreased from the 180 days value, approaching that recorded at baseline. CONCLUSIONS: Although this study provides no evidence for the long-term benefit of antioxidants in ARM, the results suggest that increasing the level of retinal antioxidants might influence macular function early in the disease process, as well as in normal aging.
Abstract: PURPOSE: Visual flicker induces a response in human optic nerve blood flow (F(onh)) and inner retinal activity, as assessed by laser Doppler flowmetry and electroretinogram (ERG), respectively. In this study the relationship was examined between the flicker-evoked changes in F(onh) (RF(onh)) and ERG when various parameters of the stimulus were varied. METHODS: In five normal observers (mean age, 41; range, 25-62 years) F(onh) and ERG were recorded simultaneously in response to pure red (R) or pure green (G) flicker, as well as heterochromatic R-G flicker (30 degrees field at the posterior pole). RF(onh) and the changes in the first (1F) and second (2F) harmonic amplitudes of the ERG were documented as a function of the frequency of pure luminance and equiluminant R-G flicker, the mean illuminance of 10-Hz luminance flicker, and the color ratio r = R/(R + G) of a 15-Hz heterochromatic R-G flicker. RESULTS: Frequency-dependent changes in RF(onh) were similar to those in both 1F and 2F amplitudes for equiluminant R-G flicker. RF(onh) and 2F amplitude increased and then saturated with increasing mean illuminance of luminance flicker. They both decreased similarly as the R-G flicker approached the r value corresponding to equiluminance. RF(onh) was positively correlated with both 1F and 2F amplitudes (r = 0.55 and 0.31, respectively, P < 0.05) when these quantities were recorded as a function of frequency of R-G equiluminant flicker. RF(onh) was positively correlated with 2F amplitudes when both quantities were recorded as a function of mean illuminance of luminance flicker and r of heterochromatic R-G flicker (r = 0.52 and 0.48, respectively, P < or = 0.01). CONCLUSIONS: Under specific experimental conditions, changes in human RF(onh) are similar to and correlated with those of the flicker ERG 1F and 2F amplitudes. These findings support a relationship between vaso- and neural activity changes in the neural tissue of the human eye.
Abstract: We investigated the effects of photoreceptor degeneration on the anatomy and physiology of inner retinal neurons in a mouse model of retinitis pigmentosa, the retinal degeneration (rd) mutant mouse. Although there is a general assumption that the inner retinal cells do not suffer from photoreceptor death, we confirmed major changes both accompanying and after this process. Changes include sprouting of horizontal cells, lack of development of dendrites of rod bipolar cells, and progressive atrophy of dendrites in cone bipolar cells. Electrophysiological recordings demonstrate a selective impairment of second-order neurons that is not predictable on the basis of a pure photoreceptor dysfunction. Our data point out the necessity to prove integrity of the inner retina before attempting restoring visual function through photoreceptor intervention. This is even more important when considering that although intervention can be performed before the onset of any symptoms in animals carrying inherited retinopathies, this is obviously not true for human subjects.
Abstract: PURPOSE: To evaluate recovery of pattern visual evoked potentials (VEPs) after macular bleaching in patients with Stargardt's disease-fundus flavimaculatus (STD/FF). METHODS: Sixteen unrelated patients with STD/FF (age, 26-52 years; visual acuity, 0.2-1.0; phenotype I, n = 6; phenotype II, n = 8; or phenotype III, n = 2) and 15 age-matched control subjects were evaluated. VEPs were recorded in response to counterphased (two reversals per second) checkerboards (check size, 15 minutes; mean luminance, 80 cd/m(2); contrast, 80%; stimulus field size, 18 degrees ) in baseline condition and at 20, 40, and 60 seconds after a 30-second exposure to a bleaching light (3.58 log photopic trolands), presented to the central (6 degrees field) retina. In all patients, macular focal electroretinograms (FERGs) to an 18 degrees uniform field, flickering at 41 Hz, were also recorded in separate sessions. RESULTS: At every postbleaching time, VEPs were delayed and suppressed in amplitude, compared with prebleaching values, in both patients and control subjects. However, the amount of delay and suppression was, on average, more pronounced (P < 0.001) in patients than in control subjects. This difference was not accounted for by eccentric fixation in patients (n = 8) with central scotoma and was still substantial when only patients (n = 8) with normal visual field and acuity were considered. In individual patients, baseline FERG amplitudes correlated (r = -0.6, P < 0.01) with the suppression of VEP amplitude at 40-seconds after bleaching. CONCLUSIONS: The results indicate an altered recovery of pattern VEPs after macular bleaching in STD/FF and suggest adaptation abnormalities in macular cone photoreceptors, occurring at disease stages with relatively preserved central visual field and acuity.
Abstract: Two genetically engineered strains of mice were used to characterize murine cone function electroretinographically, without interference of rod-driven responses: (1) mice with a deletion of the gene for the rod transducin alpha-subunit (transducin alpha-/-), and (2) mice with rod arrestin deleted (arrestin -/-). In the first three months of age, both strains have a normal complement of rods and normal rod structure, but transducin alpha-/- mice have no rod-driven responses to light, while rod-driven activity of arrestin -/- mice can be suppressed by a single intense flash for hours. In response to intense flashes the electroretinograms of these strains of mice showed a readily identifiable, pure-cone a-wave of approximately 10 microV saturating amplitude. A 530 nm background that saturates rod responses of wild type mice was found to desensitize the b-wave responses of mice of both transgenic lines, whether the b-waves were driven by photons captured by M- or UV-cone pigments. The desensitizing effect of the 530 nm background on UV-pigment driven responses provides new evidence in support of the hypothesis of functional co-expression of the M-pigment in cones expressing primarily the UV-pigment.
Abstract: BACKGROUND: The relationship between the flicker-evoked changes in optic nerve blood flow (F onh ) and neural retinal activity was investigated by laser Doppler flowmetry and electroretinogram (ERG), respectively. MATERIAL AND METHODS: In five normal subjects F onh was continuously recorded before, during and after exposure to green flicker modulation (30 degrees field at the posterior pole), at different levels of mean illuminance between 0.9 and 13.5 lux. During flicker stimulation, ERGs were simultaneously recorded with F onh. The flicker-evoked changes in F onh ( RF onh ) and the amplitudes of the first (1F) and second (2F) harmonic component of the ERG were measured. RESULTS: By increasing mean flicker illuminance, RF onh and ERG 2F, but not 1F amplitude first increased and then saturated beyond 10 lux. RF onh and the corresponding 2F amplitudes, recorded at the various mean illuminances, showed a significant positive correlation (r = 0.79, p < 0.01). CONCLUSIONS: Under specific experimental conditions, changes in human RF onh are quantitatively correlated with those of the flicker ERG 2F amplitudes. Since the 2F component reflects, unlike 1F, a strong contribution from inner retina, the present findings support the presence of an association between vasoactivity and inner retinal activity changes in the human eye. This finding may provide a new approach to the study of neuro-ophthalmic disorders.
Abstract: The results from literature concerning some aspects of retinal function in macular degenerations (MDs) were reviewed in order to evaluate whether (a) specific patterns of retinal dysfunction may be linked to different clinical phenotypes, and (b) distinct functional profiles may help in orienting molecular diagnosis of diseases. Examined clinical phenotypes included: Stargardt disease/fundus flavimaculatus (St/FF), age-related maculopathy (ARM) and macular degeneration (AMD), pattern dystrophies (PD), Best vitelliform dystrophy (BVD), Sorsby's fundus dystrophy (SFD), autosomal cone-rod dystrophies (CRD). The following functional tests were evaluated: (1) electroretinogram (ERG) (scotopic and photopic according to ISCEV standards, rod and cone photoresponses, rod and cone b-wave intensity-response function, focal ERGs); (2) dark adaptometry (pre-bleach sensitivity and post-bleach recovery kinetics); (3) fundus reflectometry (pigment density and regeneration kinetics). Specific patterns of retinal dysfunction were identified for St/FF, ARM/AMD, SFD and BVD, whereas partially overlapping profiles were found for PD and CRD. Specific functional patterns were associated with different peripherin/RDS gene mutations, as well as with CRX mutations. Combined analysis of different retinal function tests may help to identify different phenotypes of MD, and to orient molecular diagnosis for selected genotypes.
Abstract: PURPOSE: To determine the response of human optic nerve head (ONH) blood flow (delta F) to heterochromatic equiluminant flicker modulation (eql-fl) and compare it to the response induced by pure luminance flicker (l-fl). METHODS: In 5 normal volunteers the ONH blood flow was measured by conventional laser Doppler flowmetry. Stimuli were generated by green and red light emitting diodes and delivered to the eye through a fundus camera illumination optic. Both green and red illuminances were square wave modulated in counter phase at different frequencies between 2 and 40 Hz. delta F was defined as the ratio between the ONH blood flow after 1 min stimulation and a baseline blood flow measured prior to the stimulation. RESULTS: In response to a 2 Hz eql-fl, ONH blood flow increases by 36% in average. delta F versus flicker frequency displayed the characteristics of a low-pass function with a cutoff frequency of 10 Hz for an eql-fl and a band-pass function with broad maximum around 10 Hz for the I-fl. CONCLUSIONS: delta F in human ONH can be evoked by heterochromatic equiluminant flicker modulation. The blood flow frequency response to eql-fl and I-fl are similar to the neural activity dominated by the Parvo- and Magno-cellular activity, respectively. These findings offer a new approach to study the neurovascular coupling at the ONH in both physiological and diseased conditions involving predominantly or selectively the Magno- and Parvo-pathways.
Abstract: PURPOSE. To determine the response of human optic nerve head blood flow (R:F(onh)) to heterochromatic equiluminant flicker modulation and compare it to the response induced by pure luminance flicker. METHODS. In five normal volunteers, F(onh) measured at the neuroretinal rim was monitored continuously by laser Doppler flowmetry. Stimuli were generated by green and red light emitting diodes and delivered to the fundus in Maxwellian view (field of 25(o)). Both green (G:) and red (R:) illuminances were square-wave modulated, 180(o) out of phase, with a maximum value of 10.4 for G: and 2.64 lux for R: Flicker frequency was varied from 2 Hz to 40 Hz. R:F(onh) was defined as the change in F(onh) during stimulation relative to the prestimulus F(onh). RESULTS. Defining the color ratio r as R:/(R: + G:), the R:F(onh), measured for a 15-Hz flicker, was largest at pure luminance (r = 0 and 1), declined at mixed luminance and chromatic modulations, and reached a secondary maximum at r = 0.45, the value of psychophysical equiluminance. R:F(onh) versus flicker frequency displayed the characteristics of a low-pass function for the equiluminance flicker stimulus and of a band-pass function, with a maximum at intermediate frequencies, for the luminance flicker stimulus. CONCLUSIONS. R:F(onh) in humans can be evoked by heterochromatic flicker, modulated either in luminance or chromatic equiluminant conditions. R:F(onh) may be specific for luminance and chromatic modulations, similar to neural responses dominated by the magno- and parvocellular activity, respectively. These findings offer a new approach to study the neurovascular coupling at the optic nerve head in both physiological and diseased conditions involving predominantly or selectively the magno- and parvocellular pathways.
Abstract: PURPOSE: To quantify the relationship between optic nerve head tomography and perimetric sensitivity in patients with papilledema. METHODS: Eight patients with variable degrees of recently diagnosed papilledema associated with idiopathic intracranial hypertension (IIH) were evaluated with confocal scanning laser ophthalmoscopy (CSLO) and automated perimetry. Patients were followed up with serial measurements over a period of 5 to 30 months (mean +/- SD, 17.1 +/- 9), while under medical treatment (acetazolamide). The tomographic parameters, volume above reference (VAR), volume above surface (VAS), effective mean height (EMH), and maximum height in contour (MxHC), were obtained by tomography, either globally or from predefined disc sectors. The perimetric indices, mean deviation (MD) and pattern SD (PSD), were evaluated. The results from patients' right eyes and the individual intereye differences in both tomographic and perimetric parameters, were statistically evaluated by nonparametric correlational (Spearman) and repeated measures (Wilcoxon) analyses. RESULTS: At baseline, all tomographic parameters were negatively correlated with MD in global (r = -0.8) and sectorial (r = -0.6) evaluations. The interocular differences in overall tomographic parameters were correlated with corresponding differences in perimetric MD (r = -0.8) and PSD (r = 0.6). During the follow-up period, volumetric disc parameters decreased (P < 0.02), whereas perimetric MD increased (P = 0.02) at comparable times. CONCLUSIONS: In patients with recently diagnosed papilledema, optic nerve head tomographic abnormalities are quantitatively correlated with visual field sensitivity losses. Therapeutic improvement of volumetric parameters may be paralleled by recovery in perimetric sensitivity. The data support the possible use of both techniques in combination to monitor the amount of papilledema and the effectiveness of treatments designed to reduce intracranial hypertension.
Abstract: PURPOSE: To evaluate retinal, cone-mediated flicker sensitivity (CFS) in age-related maculopathy (ARM) by quantifying response gain and threshold of the focal electroretinogram (FERG) to flicker modulation. METHODS: Nineteen patients with ARM (visual acuity > or =20/30) and 11 age-matched control subjects were examined. Twelve patients had less than 20 soft drusen in the macular region and no hyper-/hypopigmentation (early lesion), whereas seven had more than 20 soft drusen and/or focal hyper-/hypopigmentation (advanced lesion). Macular (18 degree ) FERGs were elicited by a sinusoidally flickering (41 Hz) uniform field (on a light-adapting background) whose modulation depth was varied between 16.5% and 94%. Amplitude and phase of the response's fundamental harmonic were measured. RESULTS: In both control subjects and patients with ARM, log FERG amplitude increased with log stimulus modulation depth with a straight line (power law) relation. However, the slope (or gain) of the function was, on average, steeper in control subjects than in patients with either early or advanced lesions. Mean FERG threshold, estimated from the value of the log modulation depth that yielded a criterion response, did not differ between control subjects and patients with early lesions but was increased (0.35 log units) compared with control subjects in those with advanced lesions. In both patient groups, but not in control subjects, mean FERG phase tended to delay with decreasing stimulus modulation depth. CONCLUSIONS: Retinal CFS losses can be detected in ARM by evaluating the FERG as a function of flicker modulation depth. Reduced response gain and phase delays, with normal thresholds, are associated with early lesions. Increased response thresholds, in addition to gain and phase abnormalities, may reflect more advanced lesions. Evaluating CFS by FERG may directly document different stages of macular dysfunction in ARM.
Abstract: PURPOSE: To evaluate in glaucomatous eyes the photopic electroretinogram (ERG) negative response (PhNR), a component that follows the b-wave peak and is thought to be correlated with inner retinal activity. METHODS: Eleven patients with open-angle glaucoma (OAG) and moderate field loss (Humphrey 30-2 [Humphrey Instruments, San Leandro, CA] mean deviation < or = -6 dB), eight with ocular hypertension (OHT), and eight age-matched normal subjects were tested. Optic discs of patients and control subjects were evaluated by confocal scanning laser ophthalmoscopy. ERGs were recorded to long-duration stimuli (250 msec) of photopic luminance (78 candelas [cd] /m2), presented in the macular region (12 degrees x 12 degrees field size) on a steady, adapting background. Amplitudes of the a-wave and b-wave and the PhNR were measured. Pattern reversal ERGs to 30-minute checkerboards were also recorded from patients and control subjects. RESULTS: Compared with control subjects, patients with OAG showed reduced PhNR (average reduction: 62%, P < 0.01), but normal a- and b-wave amplitudes. In patients with OHT, PhNR and a- and b-wave amplitudes did not differ from control values. In individual patients with OAG, PhNR amplitudes were correlated positively with pattern ERG amplitudes (r = 0.80; P < 0.01) and central (12 degrees) perimetric mean deviations (r = 0.68; P < 0.05) and negatively with cup-to-disc area ratios (r = -0.79; P < 0.01) and cup shape measures (r = -0.78; P < 0.01). CONCLUSIONS: Similar to that found in monkeys with experimentally induced glaucoma, the PhNR is selectively altered in human glaucoma. The correlation between PhNR losses and clinical parameter abnormalities suggests that this component depends on inner retina integrity and may be of clinical value for detecting glaucomatous damage.
Abstract: PURPOSE: Laser Doppler measurements performed immediately after the transition from dark adaptation (DA) to light led to the hypothesis that retinal blood flow, Fret, is increased during DA, but the use of visible lasers had prevented measurements during DA. Our aim was to test this hypothesis by measuring Fret during and after DA. MATERIAL AND METHODS: Fret in retinal vessels at the optic disk surface was recorded quasi-continuously in one eye of 6 normal subjects (age 27 to 60 years) using a laser Doppler flowmeter in the near-infrared (810 nm). Measurements were performed during light (baseline), various periods of DA and again during light. DA lasted between 2 and 32 min. RESULTS: Average Fret for the 6 subjects did not change significantly (-2.7 +/- 8% sd, p > 0.05) during the various periods of DA, as determined from linear regressions of the flux versus time. Following the transition from DA to light, there was, in most cases, a rapid transient increase of the flux, which reached an average value of 37 +/- 10% above the pre-transition value and peaked at 30-60 sec after the transition. CONCLUSIONS: These results do not support the hypothesis that Fret in normal volunteers is increased during DA. Rather, they strongly suggest that the transient increase in flux observed after DA is induced by the transition from dark to light (FNSRS #3200-043157 et CNR, It. #95.01715.CT04).
Abstract: BACKGROUND: The aim of this study was to evaluate the focal electroretinogram (FERG), an objective indicator of outer retinal function, in nonexudative age-related macular degeneration (NE-AMD), and to compare FERG results with morphological lesions assessed by stereoscopic fundus photographs and fluorescein angiograms. METHODS: Twenty-five patients (25 eyes) with bilateral NE-AMD (visual acuity of the study eyes > or = 0.4) as well as 10 age- and sex-matched control subjects (10 eyes) were evaluated. FERGs were recorded from the macular region (9 degrees) in response to sinusoidal stimuli flickered at 32 Hz. Amplitude and phase angle of the Fourier-analyzed FERG fundamental component were measured. Fundus lesions were graded from color slides according to the Wisconsin age-related maculopathy grading system . Fluorescein angiograms were evaluated by an image analysis technique to compute the area with pathological hyperfluorescence (associated with drusen and/or retinal pigment epithelial atrophy) within the macular (approximately 9 degrees x 9 degrees) region. RESULTS: Compared to control eyes, NE-AMD eyes had a reduction in the mean FERG amplitude (57% loss, P<0.001) with no phase changes. Amplitudes of individual affected eyes were negatively correlated with either the Wisconsin grading score (r = -0.63, P < 0.001) or the percentage area of pathological hyperfluorescence (r = -0.70, P<0.01). Eyes with minimal NE-AMD lesions (Wisconsin score < or = 6) and normal acuity had a lower mean amplitude (47% loss, P < 0.05) than that of control eyes. CONCLUSIONS: The results indicate that, in NE-AMD, the FERG is altered in parallel with the extent and severity of fundus lesions. However, a functional impairment of outer macular layers, which is detected by FERG losses, could precede morphological changes typical of more advanced disease.
Abstract: PURPOSE: To evaluate the correlation of pattern electroretinogram (PERG), an index of inner retinal function, with confocal scanning laser (CSLO) optic disc structural parameters in ocular hypertension (OHT). METHODS: Thirty-four patients with OHT, normal white-on-white (Humphrey 30-2) perimetry, and normal clinical optic discs were examined with PERG and CSLO disc analysis. Two groups of normal subjects (n = 38 and 18, for PERG and CSLO, respectively) and a group of 12 patients with early open-angle glaucoma (EOAG) were also tested. Pattern electroretinogram amplitudes were measured in response to sinusoidal gratings of variable spatial frequency (0.58-5.8 cycles/degree), modulated in counter-phase at 7.5 Hz. Morphometric optic disc parameters were obtained by the Heidelberg Retina Tomograph (HRT), either globally or from predefined disc sectors. In addition to standard parameters, the cup shape measure, an index of depth variation and steepness of the cup walls, was determined. RESULTS: In individual OHT patients, PERG amplitudes at 2.6 cycles/degree were negatively correlated with cup shape measures (r = -0.43, P < 0.01) obtained from analysis of the inferotemporal (IT) sector. No significant correlations were found for the other parameters. On average, the cup shape measures derived from IT sector or global analysis were significantly (P < 0.01) worse, and closer to the measures of EOAG patients, in OHT patients with abnormal PERG compared with those with normal PERGs. The cup shape measure displayed a low sensitivity (20%) and a high specificity (100%) in predicting PERG abnormalities in individual OHT patients. CONCLUSIONS: The results indicate that in OHT there is a significant although weak correlation between PERG amplitude and the shape of the optic disc cup, suggesting a parallel involvement of both function and morphology. Combined PERG and optic disc cup structural analysis is of potential diagnostic value to detect early damage to optic nerve head in individual OHT patients.
Abstract: OBJECTIVES: The flicker electroretinogram (FERG) consists mainly of a linear (fundamental, 1F) and a non linear (second harmonic, 2F) component. Previous results indicate that 2F originates more proximally in the retina than 1F, and that retinitis pigmentosa (RP) may affect 2F to a greater extent than 1F. The aim of this study was to evaluate FERG 1F and 2F abnormalities in RP as a function of the stimulus temporal frequency (TF). METHODS: Twelve patients with typical RP and 10 age-matched controls were examined. FERGs were recorded in response to uniform fields (18 degrees) presented in the macula on a light-adapting background. Stimuli were flickered sinusoidally at different, closely spaced TFs between 3.7 and 52 Hz. Amplitudes and phases of the Fourier analysed 1F and 2F components were measured. Components' apparent latencies were estimated from the rate at which phase lagged with TF. RESULTS: When compared to controls, mean 1F amplitudes of patients were reduced at both low (3.7-12.6 Hz) and high (14-52 Hz) TFs, with greatest losses (0.5 log units) around the peaks (3.7 and 41 Hz) of the normal TF function. Mean 2F amplitudes were reduced mainly at low TFs, with greatest losses (0.5 log units) at 5-8 Hz. On average, the shape of the 2F, but not 1F amplitude versus TF function, differed between patients and controls, showing a selective attenuation at low TFs. Mean 1F apparent latencies were delayed at both low and high TFs, with greater delays at low (85 ms) than at high (33 ms) TFs. Mean 2F apparent latencies were delayed only at low TFs (58 ms). CONCLUSIONS: In RP, 1F and 2F phase delays as well as 2F amplitude losses are dependent on TF, suggesting that FERG generators' subpopulations in both distal and proximal retina are differentially affected. Analysis of the FERG TF response is potentially useful to characterize cone system dysfunction in different genetic subtypes of RP.
Abstract: Nasal and temporal hemifield (14 x 24 degrees) pattern electroretinograms (PERGs) were recorded in eight patients (age range: 21-72 years) suffering from different post-geniculate lesions (documented by CT scan and/or MRI of the brain) and homonymous hemianopia at visual field testing. In total eight age-matched normal subjects served as controls. PERGs were elicited by alternating, sinusoidal gratings (90% contrast), whose spatial and temporal characteristics, 6 Hz-5 c deg-1 and 15 Hz-0.58 c deg-1, were chosen to enhance the relative contributions of parvo- (P) and magno- (M) retinal ganglion cell (GC) subsystems, respectively. Amplitudes and phases of the Fourier analyzed PERG 2nd harmonics were measured. In normal subjects, PERG amplitudes to 15 Hz-0.58 c deg-1, but not those of the 6 Hz-5 c deg-1 stimuli were on average larger (P < 0.05) in nasal than in temporal hemiretinae. In hemianopic patients, PERG amplitudes of 6 Hz-5 c deg-1 stimuli were on average reduced (P < 0.05) in the hemiretinae corresponding to blind hemifields, in comparison to those in the hemiretinae corresponding to functional hemifields. No differences between hemiretinae were observed for responses of the 15 Hz-0.58 c deg-1 stimuli. In both normal subjects and patients, average PERG phases did not differ between hemiretinae, while changing significantly (P < 0.01) across stimulus conditions. The PERG naso-temporal asymmetries observed in normal subjects are consistent with the reported asymmetries in GC density observed histologically (Curcio & Allen. (1990). Journal of Comparative Neurology, 300, 5-25). The results in patients indicate that the PERGs to specific spatio-temporal stimuli (i.e. of relatively low-temporal and high-spatial frequency), presented in the hemianopic field, are reduced in amplitude. This suggests, in agreement with the experimental findings in monkeys (Cowey & Stoerig. (1991). Trends in Neuroscience, 14, 140-145), that retrograde trans-synaptic dysfunction of P-GCs, with relative sparing of the M-subsystem, may occur in humans following lesions of post-geniculate pathways.
Abstract: In normal subjects, the steady-state electroretinogram in response to contrast reversing gratings (PERG), is spatially band-pass tuned in amplitude, with a maximum at intermediate spatial frequencies and an attenuation at lower and higher ones. The amplitude attenuation at low spatial frequencies is believed to reflect centre-surround antagonistic interactions in the receptive fields of inner retinal neurons. The aim of this study was to evaluate the PERG spatial tuning in multiple sclerosis (MS) patients without a previous optic neuritis history. Steady- state PERGs in response to counterphase-modulated (8 Hz) sinusoidal gratings of variable spatial frequency (0.6, 1.0, 1.4, 2.2 and 4.8 c/deg), were recorded from 18 patients with definite or probable MS and no history of optic neuritis (ON-). Nine of them had no signs of subclinical optic nerve demyelination (asymptomatic) in either eye, while nine had symptoms or signs of optic pathways involvement (symptomatic) in one or both eyes. Results were compared with those obtained from 10 MS patients with a previous history of optic neuritis (ON+) in one or both eyes, as well as from 21 age-matched controls. The amplitudes and phases of the responses' 2nd harmonics were measured. Compared with the controls, asymptomatic ON- patients showed selective losses in mean PERG amplitudes at medium and high (1.0-4.8 c/deg) spatial frequencies. Symptomatic ON- patients and ON+ patients had reductions in mean PERG amplitudes, with respect to controls, involving the whole spatial frequency range, but with greater losses at medium-high (1.0-4.8 c/deg) than at lower spatial frequencies. In all patients' groups, the average PERG spatial tuning function differed significantly from that of the controls, assuming a low-pass instead of the normal band-pass shape. The PERG phase was delayed in ON+ but not in ON- patients, as compared to controls. However, the phase delay was independent of spatial frequency. In both ON- and ON+ patients, losses in PERG amplitude and spatial tuning tended to be associated with corresponding abnormalities in perimetric sensitivity, visual acuity, colour vision and transient visual evoked potential (VEP) latency. The results indicate that abnormalities of the spatial tuning of steady-state PERG can be found in MS patients without either optic neuritis or signs of subclinical optic nerve demyelination. These changes may reflect a retinal dysfunction, developing early in the course of MS, due to a loss of specific subpopulations of inner neurons, changes in lateral interactions of their receptive fields, or both.
Abstract: Molecular biological, histological and flicker electroretinographic results have established that mice have two cone photopigments, one peaking near 350 nm (UV-cone pigment) and a second near 510 nm [midwave (M)-cone pigment]. The goal of this investigation was to measure the action spectra and absolute sensitivities of the UV-cone- and M-cone-driven b-wave responses of C57BL/6 mice. To achieve this goal, we suppressed rod-driven signals with steady or flashed backgrounds and obtained intensity-response relations for cone-driven b-waves elicited by narrowband flashes between 340 and 600 nm. The derived cone action spectra can be described as retinal1 pigments with peaks at 355 and 508 nm. The UV peak had an absolute sensitivity of approximately 8 nV/(photon microm2) at the cornea, approximately fourfold higher than the M peak. In an attempt to isolate UV-cone-driven responses, it was discovered that an orange conditioning flash (lambda > 530 nm) completely suppressed ERG signals driven by both M pigment- and UV pigment-containing cones. Analysis showed that the orange flash could not have produced a detectable response in the UV-cone pathway were their no linkage between M pigment- and UV pigment-generated signals. Because cones containing predominantly the UV and M pigments have been shown to be located largely in separate parts of the mouse retina (), the most probable linkage is coexpression of M pigment in cones primarily expressing UV pigment. New histological evidence supports this interpretation (). Our data are consistent with an upper bound of approximately 3% coexpression of M pigment in the cones that express mostly the UV pigment.
Abstract: In this article, the methodologies and clinical applications of two electrophysiological tests, the focal electroretinogram (FERG) and the visual evoked potentials (VEPs) after photostress, are described. These techniques provide somewhat complementary results about macular function because they tap the activity of different neural substrates along the pathway of the cone system and allow evaluation of the macular function under steady-state (ie, the FERG) or dynamic (ie, the VEPs after photostress) conditions. The results obtained in patients with different macular pathologies indicate that while the FERG provides direct information about the extent and sites of macular dysfunction, the VEPs after photostress represent an objective, although not specific, index of the dynamic properties of macular performance after exposure to intense light stimulation. The combined use of both techniques appears to be promising for gaining further insights into the diagnosis and pathophysiology of macular diseases.
Abstract: It is known that changes in pattern electroretinogram (PERG) and optic disk morphology may both precede the onset of visual field damage in glaucomatous disease. However, the relationship between PERG and optic disk morphometry in ocular hypertension (OHT) has not yet been evaluated in detail. This study of PERG amplitude in a group of OHT patients indicates its significant correlation with various optic disk morphometric parameters, in particular, those of optic disk sectors considered at risk for early glaucomatous damage. Analysis of individual data points to the possibility that, while functional abnormalities may often precede optic disk morphologic changes, in a much lower number of cases it seems to be the other way around.
Abstract: The authors discuss the technical problems commonly encountered in the design of devices used in the functional analysis of the central retina (macula) and its neuronal elements. They present a simple effective solution for introducing some of the most recent and interesting results of neurophysiological and psychophysical research into the eye clinic.
Abstract: PURPOSE: To understand whether laser photocoagulation of the retina for the treatment of diabetic retinopathy (DR) alters directly or indirectly the function of the macular region. METHODS: Transient pattern electroretinograms (PERGs) to 30' checks have been recorded in DR patients before and 7-10 days after one treatment session (established protocol with Argon laser) of either the peripheral retina (panretinal treatment) or the central retina (paramacular focal treatment). RESULTS: Treatment of the peripheral retina causes, in most eyes, a small increase (about 15% on average) of the PERG amplitude. Focal paramacular treatment causes a marked decrement (about 40% on average) of the PERG amplitude. Simulated retinal amputation induced by focal treatment, obtained by means of adequate stimulus masking, resulted in a 15-20% PERG decrement only. CONCLUSIONS: The PERG increase after peripheral treatment may be due to rearrangement of both retinal and choroideal hemodynamics and does not necessarily result in useful long term changes. The PERG decrease after focal, paramacular treatment is far larger than that expected on the basis of the amputated area only. This may result from thermal and/or toxic damaging effects spreading outside the treated area. The results are relevant for both a better monitoring of central retinal function in the course of laser treatment and a better evaluation of the cost/benefit ratio after photocoagulation in DR.
Abstract: PURPOSE: It is known that the pattern electroretinogram (PERG) of normal subjects is reduced temporarily after short-term elevation of intraocular pressure (IOP). The authors evaluated PERG changes in ocular hypertension during and after transient IOP elevation. METHODS: Steady state (8 Hz) PERGs to sinusoidal gratings (1.7 cyc/deg spatial frequency) were recorded in seven untreated patients with ocular hypertension at medium risk (maximum IOP, 22 to 25 mm Hg; cup-disk ratio, 0.6 to 0.7; normal Humphrey 30-2 visual field results; positive family history), as well as in six age-matched normal subjects. Recordings were obtained for the baseline condition during a short-term (6-minute) IOP elevation (to 30 mm Hg) by using a suction cup apparatus and during a 6-minute recovery period after removal of the apparatus. RESULTS: During IOP elevation, PERG amplitudes were reduced significantly from baseline values in normal subjects and patients. However, PERG losses were significantly greater in patients (average loss from baseline after 4 minutes of IOP elevation: 72% +/- 7.6%) compared to controls (average loss after 2 minutes of IOP elevation: 40% +/- 7.5%). In the recovery phase, mean PERG amplitude returned to baseline values in normal subjects but not in patients, whose recovery took longer. In normal subjects, PERG phase did not change either during or after IOP elevation. In patients, however, PERG phase showed a delay from baseline during and after IOP elevation (average delay after 6 minutes of recovery: -41.1 degrees +/- 13 degrees). CONCLUSIONS: Results indicate that increasing IOP with scleral suction produces greater PERG losses in eyes with ocular hypertension than in normal eyes. This suggests that the inner retina of eyes with ocular hypertension may have a heightened sensitivity to vascular or mechanical changes induced by transient IOP elevation.
Abstract: Steady-state pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) in response to sinusoidal gratings (2 c/deg), sinusoidally counterphased at closely spaced temporal frequencies (TFs) between 4 and 28 Hz, were recorded from 11 patients with unilateral optic neuritis (ON; 11 affected eyes and 10 healthy fellow eyes) and 7 age-matched normal subjects (7 eyes). Amplitude and phase of responses' second harmonics were measured. Responses' apparent latencies were estimated from the rate at which phase lagged with TF. When compared to control values, mean PERG and VEP amplitudes of ON eyes were reduced (by about 0.4 log units) at both low (5-10 Hz) and high (16-20 Hz) TFs. Mean PERG amplitudes of fellow eyes were selectively reduced at low TFs (by about 0.3 log units). Mean PERG apparent latencies of both ON and fellow eyes were delayed (by 15 and 9 ms, respectively). Mean VEP apparent latency of ON eyes was delayed at both low and high TFs (by 24 and 30 ms, respectively), while that of fellow eyes was selectively delayed at high TFs (by 28 ms). The results in ON eyes indicate non-selective abnormalities of PERG and VEP generators responding at both low and high TFs. VEP TF losses may be in part accounted for by corresponding PERG losses. In the fellow eyes of patients, more selective PERG and VEP TF abnormalities may suggest differential impairment of retinal and postretinal subsystems responding better to low and high TFs (i.e. parvo- and magnocellular streams).
Abstract: PURPOSE. The aim of this study was to evaluate the function of the neurosensory retina in Best vitelliform macular dystrophy (BMD) by recording the focal electroretinogram (ERG) fundamental and 2nd harmonic components, which are known to be dominated by receptoral and postreceptoral activity, respectively. METHODS. FERGs were recorded in response to a uniform field (9 x 9 deg) flickered sinusoidally at either 8 Hz or 32 Hz (peak frequencies for the 2nd and fundamental harmonic, respectively). The fundamental component of the response to the 32-Hz stimulus and the 2nd harmonic of the response to the 8-Hz stimulus were measured in their amplitudes and phases. The fundamental-2nd harmonic amplitude ratio was taken as an index of the relative changes in the FERG components. Eleven patients with BMD and vitelliform stage macular lesions were evaluated. Results were compared with those obtained from 13 patients with Type 2 Stargardt macular dystrophy (STD) according to the Noble and Carr Classification, and 29 normal control subjects. Four BMD and four STD patients were also followed electrophysiologically over a 48 month period. RESULTS. Compared to controls, BMD patients showed losses of both FERG fundamental and 2nd harmonic amplitudes, and an increase in the fundamental and increase in the fundamental-2nd harmonic ratio. STD patients also showed losses of both fundamental and 2nd harmonic, but the fundamental-2nd harmonic ratio was normal. In BMD patients, but not in those with STD, the fundamental amplitude tended to decrease over the follow-up period. CONCLUSIONS. The results indicate that BMD involves neurosensory abnormalities early in the disease process. The increased fundamental-2nd harmonic ratio suggests that a postreceptoral dysfunction may be present in addition to that of photoreceptors. This differs from STD, where losses appear to affect primarily the receptoral retina. Receptoral losses in BMD may progress throughout the medium-term follow up.
Abstract: BACKGROUND--Osteo-odontokeratoprosthesis (OOKP) is an autologous transplantation procedure in which the cornea is replaced by an optical cylinder glued to a biological support. Patients undergoing OOKP surgery may develop a secondary glaucoma whose diagnosis, by means of standard diagnostic procedures, is often doubtful. METHODS--In the present study pattern electroretinograms (PERGs), visual evoked potentials (VEPs), contrast sensitivity, and automated threshold perimetry (Humphrey 30-2) were evaluated in 19 OOKP treated patients with postoperative visual acuities > or = 0.8. Nine patients had had a preoperative secondary glaucoma, while the remaining 10 had no history of glaucoma and normal posterior pole. RESULTS--Results were compared with those obtained from either normal control subjects or from ordinary glaucoma patients. PERG amplitudes and contrast and perimetric sensitivities were reduced in both groups of OOKP patients when compared with normal controls. However, these losses were significantly greater in OOKP patients with glaucoma compared with those with normal posterior pole. VEPs were reduced, compared with controls, only in OOKP patients with glaucoma. These VEP losses were similar to those found in ordinary glaucoma patients. CONCLUSION--Among the tests employed, VEPs showed the best accuracy (79%) in discriminating between glaucomatous and non-glaucomatous OOKP treated eyes. The present results suggest a possible use of the VEP technique for detecting glaucomatous dysfunction after OOKP.
Abstract: We report on a young patient who suffered from diabetes mellitus and neurosensorial deafness from the age of two. One year later she was noted to have deteriorated vision and the diagnosis of optic atrophy was made, her visual acuity decreased progressively. At the age of six she was admitted to our hospital because of thiamine responsive megaloblastic anemia, a rare clinical feature of Wolfram's syndrome (only 13 cases have been reported to date). Thiamine (75 mg/day) was commenced at a single oral dose with a rapid increase of Hb level after a few days of therapy. The insulin requirement didn't decrease during thiamine therapy, the C-peptide level after glucagon remained almost indosable. No improvement was observed in the deafness and in the optic atrophy. These findings suggest that diabetes mellitus and optic atrophy, in Wolfram's syndrome are not related to thiamine metabolism.
Abstract: To investigate pattern electroretinogram changes in treated ocular hypertension, we evaluated pattern electroretinogram recordings of 48 hypertensive eyes following an 8-month timolol maleate therapy. During treatment, 27 of 48 eyes had normalized intraocular pressures (15-18 mm Hg), while 21 retained elevated values (21-25 mm Hg). Twenty-eight eyes with untreated hypertension (22-25 mm Hg) lasting at least 8 months, as well as 32 untreated, normotensive eyes served as controls. When compared to untreated normotensive controls, timolol-treated eyes with either elevated or normalized intraocular pressures showed reductions in the mean electroretinographic amplitudes. However, these amplitude reductions were substantially greater in treated eyes with elevated pressures as compared to those with normalized ones. Untreated hypertensive controls showed pattern electroretinogram reductions, with respect to normal values, that were comparable to those of treated hypertensive eyes, but larger than those of treated normotensive ones. These results indicate that, in treated ocular hypertension, pattern electroretinogram losses tend to be associated with moderately increased intraocular pressures in the range of 21-25 mm Hg. Electroretinographic abnormalities may be, at least in part, prevented only by lowering intraocular pressure into a normal range.
