Search

Objective: To report the effect of hydroxychloroquine therapy cessation on the multifocal electroretinogram (mfERG) in a case series of patients with rheumatic disease suspected to have retinopathy., Methods: Comprehensive data were retrospectively reviewed on 14 patients from a total of 50 cases who discontinued hydroxychloroquine due to suspected toxicity. Patients were followed for 4 years after the cessation of therapy. mfERG testing had been part of original screening for hydroxychloroquine retinopathy and was continued after therapy cessation at 6-month intervals. Descriptive statistics, independent sample t test, and one-way analysis of variance with repeated measures and post hoc analysis were conducted to determine patients' clinical characteristics and changes in the mfERG after therapy cessation, respectively., Results: All 14 patients were female; 12 were treated for rheumatoid arthritis and 2 for systemic lupus erythematosus. Three groups were identified: (i) 9 patients in whom the responses of the mfERG recovered to within normative values after cessation of hydroxychloroquine therapy, (ii) 3 who experienced limited recoveries, and (iii) 1 patient whose mfERG response was unchanged. There was no significant difference (p > 0.05) in the clinical characteristics of these patients. However, the proportional reduction of mfERG ring 1, 2, and 3 amplitudes from age normal responses at the time of discontinuation of drug use for the first and second groups of patients was significantly different, with more reduction in group 2 (p < 0.05)., Conclusion: Early detection of hydroxychloroquine retinopathy through screening and subsequent therapy discontinuation could result in recovery of the mfERG ring amplitude response and preservation of visual function., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

In the field of drug safety research, electroretinography (ERG) is commonly conducted according to the international standard method propounded by the International Society for Clinical Electrophysiology of Vision (ISCEV) in recent years. However, various ERG methods other than the ISCEV standard method are also utilized depending on the intended purpose of the evaluation. In this study, we investigated the availability of a multistep light stimulus method for evaluation of rod function in Long-Evans rats using sildenafil, which is known to inhibit phosphodiesterase 6 (PDE6) in phototransduction and induce visual dysfunctions in humans. Sildenafil was orally administered to female Long-Evans rats at doses of 15, 50, and 150 mg/kg, and ERG was recorded at 1.5 h after treatment. In addition to a - 2.0 log cd·s/m 2 stimulus corresponding to dark-adapted 0.01 ERG in the ISCEV standard method, light stimulus intensities of -4.5, -4.0, -3.0, -1.0, 0.0, and +1.0 log cd·s/m 2 were applied for multistep ERG recording. The amplitude and implicit time of the a-wave were decreased and prolonged, respectively, at doses of ≥50 mg/kg. The amplitude and implicit time of the b-wave were decreased and prolonged, respectively, at all doses. However, the b-wave at 15 mg/kg was only diminished or attenuated at ≤ - 3.0 log cd·s/m 2 , as weaker stimuli than dark-adapted 0.01 ERG in the ISCEV standard protocol. These findings suggest that sildenafil triggers visual dysfunctions through PDE6 inhibition, and indicate that the multistep light stimulus method is highly sensitive for detection of phototransduction abnormalities in retinal rod cells., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To investigate the efficacy and toxicity of intravitreous melphalan for treatment of retinoblastoma, as a single agent or with concomitant topotecan., Participants: A total of 130 eyes of 120 patients with retinoblastoma receiving 630 intravitreous (melphalan, topotecan) or topotecan periocular injections. A total of 83 (64%) of these eyes were treated with concomitant ophthalmic artery chemosurgery (OAC)., Design: Retrospective cohort study., Methods: Indirect ophthalmoscopy and clinical imaging were used to evaluate clinical response. Ocular survival and disease-free survival were estimated using Kaplan-Meier methods in 130 eyes. Ocular toxicity was evaluated by clinical findings and electroretinography (ERG) on 244 evaluable injections in 63 patients using 30-Hz flicker responses. Analysis was performed using linear mixed effects models with a random intercept and slope for each patient and a fixed effect for number of injections, in addition to any other fixed effect of interest., Main Outcome Measures: Ocular survival, disease-free survival, ERG: peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation., Results: There were no disease- or treatment-related deaths, and no patient developed externalization of tumor or metastatic disease. Two-year Kaplan-Meier estimates of ocular survival and disease-free survival were 94.2% (95% confidence interval, 89.2-99.4) and 86.2% (95% confidence interval, 78.7-94.5), respectively. There was a significant association between the number of injections and diminished ERG responses, such that on average each intravitreous melphalan injection was associated with a 5.3-μV decrease in ERG amplitude (P < 0.001). Concomitant intra-arterial chemotherapy (P = 0.01) and greater inherent ocular pigment also were significantly associated with a reduction in ERG (P = 0.045). Patient age and weight, new injection site location, addition of topotecan, concomitant focal treatment, and time interval between injections were not significantly associated with toxicity., Conclusions: Intravitreous melphalan is an effective treatment for vitreous seeding in retinoblastoma, resulting in high rates of ocular survival and disease-free survival. However, in this study, each injection of melphalan was associated, on average, with a decrement in ERG response. The findings suggest increased toxicity (1) when OAC is given within 1 week of the intravitreous injection and (2) in more deeply pigmented eyes., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools., Pattern of Retinopathy: Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. DOSE: We recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight., Risk of Toxicity: The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year., Major Risk Factors: High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen., Screening Schedule: A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors., Screening Tests: The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus., Toxicity: Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication., Counseling: Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate retinal toxicity in patients treated with high-dose hydroxychloroquine (HCQ) (Plaquenil, Sanofi Pharmaceuticals) for chronic graft-versus-host disease (GVHD)., Design: Cohort study., Participants: Twelve patients with chronic GVHD treated with 800 mg/day HCQ between June 2005 and December 2010., Methods: Patients in this study underwent ophthalmologic examination yearly and ancillary studies including colour vision, Amsler grid, fundus photographs, Humphrey 10-2 automated perimetry, spectral-domain optical coherence tomography (SD-OCT), and multifocal electroretinography (mfERG). Evidence of HCQ toxicity was determined by the presence of scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, and confirmed by at least 1 objective test including SD-OCT or mfERG., Results: Of the 12 patients, 7 were male and 5 were female. Mean age was 49 years. Mean best corrected visual acuity at baseline was 20/25 and remained 20/25 at final follow-up. Median duration of HCQ treatment was 22.8 months. Median adjusted daily dosage was 11.5 mg/kg/day. Seven patients developed vortex keratopathy. No signs of pigmentary retinopathy or bull's-eye maculopathy were found in any of the patients. Three patients developed retinal toxicity with scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, as well as abnormal mfERG. Retinal structure measured by SD-OCT was abnormal in 2 of the 3 patients with retinal toxicity. Colour vision measured by Ishihara plates, as well as by 100 Hue colour test, was abnormal in 2 of the 3 patients with retinal toxicity., Conclusions: High-dose HCQ in patients with GVHD was associated with higher incidence and earlier development of retinal toxicity., (Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: Assess the usefulness of second-course ophthalmic artery chemosurgery (OAC) for patients with intraocular retinoblastoma that recurred after prior OAC. This study evaluated the efficacy and toxicity of second-course OAC., Design: Single-arm retrospective study of 29 eyes of 30 patients treated with second-course OAC at Memorial Sloan Kettering Cancer Center between May 2006 and July 2013, with a median follow-up of 25.9 months., Participants: Retinoblastoma patients who underwent a course of OAC, with a minimum of 2 months of progression-free follow-up at monthly examinations, but who subsequently received additional OAC for recurrent tumor., Methods: To determine efficacy, Kaplan-Meier survival estimates were generated and the Mantel-Cox test was used to compare curves. To determine toxicity, electroretinography (ERG) amplitudes were measured in response to 30-Hz photopic flicker stimulation before and after OAC treatment; systemic adverse events were graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE 4.0)., Main Outcome Measures: For efficacy, ocular progression-free survival, ocular event-free survival (e.g., enucleation, external-beam radiation, or intravitreal melphalan), and ocular survival. For toxicity, peak-to-peak comparisons between ERG studies before and after OAC treatment and CTCAE 4.0-graded systemic adverse events., Results: Fifty percent of all recurrences were within 4.4 months and 90% were within 16 months of completion of the first course of OAC. The 2-year Kaplan-Meier ocular survival, event-free survival, and progression-free survival estimates after second-course OAC were 82.8% (95% confidence interval [CI], 60.1%-93.2%), 57.3% (95% CI, 36.1%-73.7%), and 26.5% (95% CI, 11.0%-45.0%), respectively. All eyes without vitreous seeding were progression free, whereas eyes with vitreous seeding were associated significantly with worse ocular survival after second-course OAC (P = 0.03). After second-course OAC, 90% of eyes had stable or improved ERG responses. Of all evaluable cases, there was no increased risk of systemic toxicity during the second course compared with the initial course of OAC., Conclusions: Retinoblastoma eyes requiring second-course OAC after initial OAC treatment have good salvage rates, and the treatment has an acceptable ocular and systemic toxicity profile. However, these eyes often require additional (third- or fourth-course) OAC or other treatment methods because of progression of disease after second-line OAC, particularly if vitreous seeds are present at the time of initial OAC failure., Competing Interests: No conflicting relationship exists for any author., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To compare subjective and objective clinical tests used in the screening for hydroxychloroquine retinal toxicity to multifocal electroretinography (mfERG) reference testing., Design: Prospective, single-center, case control study., Participants: Fifty-seven patients with a previous or current history of hydroxychloroquine treatment of more than 5 years' duration., Methods: Participants were evaluated with a detailed medical history, dilated ophthalmologic examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain (SD) optical coherence tomography (OCT), automated visual field testing (10-2 visual field mean deviation [VFMD]), and mfERG testing. We used mfERG test parameters as a gold standard to divide participants into 2 groups: those affected by hydroxychloroquine-induced retinal toxicity and those unaffected., Main Outcome Measures: We assessed the association of various imaging and psychophysical variables in the affected versus the unaffected group., Results: Fifty-seven study participants (91.2% female; mean age, 55.7±10.4 years; mean duration of hydroxychloroquine treatment, 15.0±7.5 years) were divided into affected (n = 19) and unaffected (n = 38) groups based on mfERG criteria. Mean age and duration of hydroxychloroquine treatment did not differ statistically between groups. Mean OCT retinal thickness measurements in all 9 macular subfields were significantly lower (<40 μm) in the affected group (P < 0.01 for all comparisons) compared with those in the unaffected group. Mean VFMD was 11 dB lower in the affected group (P < 0.0001). Clinical features indicative of retinal toxicity were scored for the 2 groups and were detected in 68.4% versus 0.0% using color fundus photographs, 73.3% versus 9.1% using FAF images, and 84.2% versus 0.0% on the scoring for the perifoveal loss of the photoreceptor ellipsoid zone on SD-OCT for affected and unaffected participants, respectively. Using a polynomial modeling approach, OCT inner ring retinal thickness measurements and Humphrey 10-2 VFMD were identified as the variables associated most strongly with the presence of hydroxychloroquine as defined by mfERG testing., Conclusions: Optical coherence tomography retinal thickness and 10-2 VFMD are objective measures demonstrating clinically useful sensitivity and specificity for the detection of hydroxychloroquine toxicity as identified by mfERG, and thus may be suitable surrogate tests., (Published by Elsevier Inc.)

Objective: In order to investigate markers of toxic injury and elucidate the mechanisms underlying methanol intoxication at the protein level, proteomics technology was applied to study variations in retinal protein expression between normal rats and rat models of methanol intoxication., Methods: Seven rats were administered saline and methanol respectively by gavage. After seven days, retinal function was assessed by electroretinography and retinal proteins were extracted and separated by two-dimensional gel electrophoresis. The gels were then stained with AgNO₃ and analyzed with Pdquest software. The differential expression of proteins was analyzed by MALDI-TOF-TOF MS, and related proteins were searched in a protein database., Results: Twenty-eight spots with significant differences were found, 24 of which were successfully identified. Specifically, there were 14 increased expression proteins, such as aldehyde dehydrogenase, tropomyosin alpha-1 chain, myosin light chain, and crystallin family proteins. There were 10 decreased expression ones, such as glyceraldehyde-3-phosphate dehydrogenase, recoverin, ATP synthase alpha subunit in rats with methanol toxicity., Conclusions: Retinal function was greatly destroyed upon methanol intoxication. Several key proteins were up- or down-regulated upon induced retinal toxicity, indicating that there are other mechanisms underlying methanol poisoning besides oxidative injury. Together, this data provides insight and knowledge for future studies in this field., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the potential toxicity of repeated intravitreal injections of bevacizumab in rabbit eyes., Design: Randomized, placebo-controlled experimental animal study., Participants: Fourteen chinchilla rabbits; 12 assigned to the experimental group and 2 assigned to the normal control group., Methods: Three sequential, biweekly, intravitreal injections of bevacizumab in doses of 2.5 mg/0.1 mL or 5.0 mg/0.2 mL were performed on each rabbit. Evaluations included intraocular pressure (IOP), aqueous flare, B-scan ultrasound, fundus photography, ultrasound biomicroscopy, electroretinography (ERG), and visually evoked potentials (VEPs) performed at baseline and during the follow-up period. The eyes were enucleated at 1 week and 4 weeks after the last intravitreal injection, and underwent light and electron microscopic evaluations, as well as testing for apoptotic activity., Results: After intravitreal injections, no changes were found by regular clinical observation and IOP tests. There was no significant difference in the anterior chamber inflammatory activity evaluated by the laser flare meter. No evidence of retinal toxicity was seen after intravitreal bevacizumab at doses of 2.5 and 5.0 mg by either ERG or flash VEPs. Electron microscopy did show the presence of inflammatory cells and some ultrastructural changes in the photoreceptor cells in the 5.0 mg experimental group 1 week after the third injection. Mild to moderate apoptosis of photoreceptors was detected in the 5.0 mg group at the same time., Conclusions: The biweekly, multiple intravitreal injections of bevacizumab did not result in evidence of toxicity in regular clinical and functional observations at both 2.5 mg and 5.0 mg doses. The 5.0 mg dose may induce transient inflammation, ultrastructural abnormalities, and apoptosis.

Objective: To evaluate the influence of short-term carotenoid and antioxidant supplementation on retinal function in nonadvanced age-related macular degeneration (AMD)., Design: Randomized controlled trial., Participants: Twenty-seven patients with nonadvanced AMD and visual acuity > or =0.2 logarithm of the minimum angle of resolution were enrolled and randomly divided into 2 age-similar groups: 15 patients had oral supplementation of vitamin C (180 mg), vitamin E (30 mg), zinc (22.5 mg), copper (1 mg), lutein (10 mg), zeaxanthin (1 mg), and astaxanthin (4 mg) (AZYR SIFI, Catania, Italy) daily for 12 months (treated AMD [T-AMD] group; mean age, 69.4+/-4.31 years; 15 eyes); 12 patients had no dietary supplementation during the same period (nontreated AMD [NT-AMD] group; mean age, 69.7+/-6.23 years; 12 eyes). At baseline, they were compared with 15 age-similar healthy controls., Methods: Multifocal electroretinograms in response to 61 M-stimuli presented to the central 20 degrees of the visual field were assessed in pretreatment (baseline) conditions and, in nonadvanced AMD patients, after 6 and 12 months., Main Outcome Measures: Multifocal electroretinogram response amplitude densities (RAD, nanovolt/deg(2)) of the N1-P1 component of first-order binary kernels measured from 5 retinal eccentricity areas between the fovea and midperiphery: 0 degrees to 2.5 degrees (R1), 2.5 degrees to 5 degrees (R2), 5 degrees to 10 degrees (R3), 10 degrees to 15 degrees (R4), and 15 degrees to 20 degrees (R5)., Results: At baseline, we observed highly significant reductions of N1-P1 RADs of R1 and R2 in T-AMD and NT-AMD patients when compared with healthy controls (1-way analysis of variance P<0.01). N1-P1 RADs of R3-R5 observed in T-AMD and NT-AMD were not significantly different (P>0.05) from controls. No significant differences (P>0.05) were observed in N1-P1 RADs of R1-R5 between T-AMD and NT-AMD at baseline. After 6 and 12 months of treatment, T-AMD eyes showed highly significant increases in N1-P1 RADs of R1 and R2 (P<0.01), whereas no significant (P>0.05) change was observed in N1-P1 RADs of R3-R5. No significant (P>0.05) changes were found in N1-P1 RADs of R1-R5 in NT-AMD eyes., Conclusions: In nonadvanced AMD eyes, a selective dysfunction in the central retina (0 degrees -5 degrees ) can be improved by the supplementation with carotenoids and antioxidants. No functional changes are present in the more peripheral (5 degrees -20 degrees ) retinal areas.

Objective: To evaluate possible functional toxicity of intravitreal Kenalog (commercial triamcinolone acetonide) in patients' retinas., Design: Observational case series., Participants: Thirty-two phakic eyes of 16 patients who had nonproliferative diabetic retinopathy and bilateral macular edema refractory to laser therapy, which had no other eye disorder and no previous ophthalmic operation., Intervention: Kenalog (4 mg/0.1 ml) was injected intravitreally to one eye, whereas the second eye served as the control. The experimental eye was chosen as the eye with worse visual acuity (VA)., Main Outcome Measures: Deterioration of electroretinogram parameters of the study eye measured at 3 months of follow-up when compared with the electroretinogram responses of the fellow, control eye and when compared with electroretinogram responses obtained before injection. Visual acuity, intraocular pressure (IOP), and eventual complications were assessed. No improvement or deterioration of VA or any increase in IOP was regarded as a secondary outcome., Results: Average maximal response amplitude ratios of the dark-adapted b-wave (treated/control eyes) of the electroretinogram were 0.93 before (P = 0.221) and 0.94 (P = 0.387) 3 months after Kenalog injection. Average ratios of the light-adapted b-wave amplitude (treated/control eyes) of the electroretinogram were 1.04 (P = 0.702) before and 0.86 (P = 0.138) 3 months after Kenalog injection. No significant differences (P>0.05) were found between the electroretinogram parameters obtained from all eyes before and 3 months after Kenalog injection. Average VAs in the treated eyes were 1.08, 0.8, and 1.0 logarithm of the minimum angle of resolution units before and 2 and 4 months after injection, respectively. Temporary elevation of IOP was found in 4 treated eyes of 4 patients (25%)., Conclusions: No electroretinographic evidence of a retinotoxic effect of intravitreal Kenalog was found in our patients.

Purpose: Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by the intracellular accumulation of cystine. Treatment involves intracellular cystine depletion with oral cysteamine. A wide spectrum of ocular pathologic features has been associated with nephropathic cystinosis. We used the largest documented cohort of patients in the world to study the posterior segment manifestations associated with infantile nephropathic cystinosis and to determine retrospectively the effect of chronic oral cysteamine therapy on the frequency of these abnormalities., Design: Cross-sectional study of a series of patients., Participants: Two hundred eight patients with infantile nephropathic cystinosis were studied at the National Institutes of Health between 1976 and 2004., Methods: All patients underwent an ophthalmic evaluation. Patients older than 11 years also underwent Humphrey static perimetry, and electrophysiological testing was performed when possible., Main Outcome Measures: Visual acuity, retina findings, visual fields, and electroretinographic (ERG) findings., Results: Pigmentary changes with retinal pigment epithelial mottling, seen as early as infancy, were the most common posterior segment manifestations. Moderate to severe constriction of the visual fields, as well as moderate to severe reduction of rod- and cone-mediated ERG responses, was seen in older patients. The frequency of retinopathy correlated directly with time not receiving oral cysteamine therapy and inversely with time receiving oral cysteamine therapy., Conclusions: Infantile nephropathic cystinosis has posterior segment complications that can contribute to significant visual handicap. Early initiation of oral cysteamine therapy can reduce the frequency of posterior segment complications in cystinosis patients.

Background: Although intravitreal ganciclovir dosages up to 500 microg have been demonstrated to be safe in some studies, other studies have shown toxic retinal effects in rabbit eyes without silicone oil at lower dosages. In current clinical practice, the same dosage of intravitreal antiviral agent is given regardless of whether there has been retinal detachment repair with silicone oil. We performed a study to investigate, in rabbit eyes following vitrectomy and silicone oil insertion, the retinal toxicity of serial intravitreal injections of ganciclovir, using dosages previously found not to produce significant toxic effects in nonvitrectomized eyes., Methods: Twenty-eight eyes of 14 New Zealand pigmented rabbits underwent pars plana vitrectomy and silicone oil insertion. One eye of each animal received an intravitreal ganciclovir injection twice weekly for 2 weeks. The other eye received 0.1 mL of normal saline as a control. Three dosages of ganciclovir (50, 100 or 200 microg/0.1 mL) were used in three groups of three to six animals. Scotopic electroretinography and histologic examination were performed 2 weeks postoperatively., Results: No differences in scotopic b-wave threshold (p = 0.23, 0.78 and 0.50 for ganciclovir dosages of 50, 100 and 200 microg/0.1 mL respectively, Mann-Whitney U test) or in light microscopy findings were noted between the treatment and control eyes at any dosage of ganciclovir. Surgical complications were observed in eight eyes; the data for these eyes were not used for analysis., Interpretation: Ganciclovir dosages of up to 200 microg/0.1 mL appear to be safe for serial intravitreal injection in rabbit eyes following vitrectomy and silicone oil insertion.

Objective: To present the clinical picture of retinal toxicity of commercial tissue plasminogen activator (tPA)., Design: Case report and literature review., Methods: Two successive intravitreal injections of tPA (50 micro g) 3 days apart with gas tamponade were given to treat a 49-year-old man with submacular hemorrhage. The adverse consequences of this treatment were monitored. A literature review of retinal toxicity of commercial tPA in animals was also done., Main Outcome Measures: Retinal findings, electroretinograph (ERG) and visual acuity testing., Results: Diffuse pigmentary alterations sparing the posterior pole, poor visual acuity after the absorption of submacular hemorrhage, reduced scotopic and photopic ERG A- and B-waves were noted., Conclusions: This is the first reported case of retinal toxicity of commercial tPA in humans that resembles the descriptions of tPA-mediated retinal toxicity in animal models. The dosage of intravitreal tPA (between 50 and 100 micro g) may be toxic to the human retina.

Weanling rats were fed three diets differing in their concentrations of the cis- and trans-isomers of alpha-linolenic acid [18:3(n-3)] for 12 mo to study the long-term effects of these fatty acids on the electroretinogram (ERG). The diets contained 18:3(n-3) in its natural form at 2.0 g/100 g total fatty acids (C group), partially isomerized 18:3(n-3) [1.3 g/100 g cis 18:3(n-3) + 0.7 g/100 g trans 18:3(n-3); cT group] and the control level of cis 18:3(n-3) with trans 18:3(n-3) [2.0 g/100 g cis 18:3(n-3) + 0.7 g/100 g trans 18:3(n-3); CT group]. The ERG and the levels of trans-isomers of the polyunsaturated fatty acids (PUFA) of retinal and hepatic phospholipids were determined after 3, 6, 9 and 12 mo of feeding the experimental diets. Dietary trans alpha-linolenic acid altered the fatty acid composition of retinal and hepatic phospholipids by significantly increasing the Delta19trans-isomer of docosahexaenoic acid. Moreover, dietary trans-isomers of alpha-linolenic acid significantly decreased the b-wave amplitude of the ERG by 9 mo of feeding. We conclude that long-term intake of small amounts of trans-isomers of alpha-linolenic acid could disturb visual function. However, further studies are required to determine the mechanisms responsible for this phenomenon.

Objective: To determine the degree of electroretinal dysfunction in a group of patients taking Vigabatrin (VGB). Additionally, to investigate the role of cumulative dosage, the role of VGB alone or in combination with other anticonvulsants, and whether recent discontinuance of VGB affects electroretinal function as measured by the electroretinogram (ERG)., Design: Retrospective, comparative case series., Participants: Forty patients (18 male, 22 female) with a mean age of 35 years were studied as three groups: the VGB multitherapy group (n = 24) included those taking VGB with other anticonvulsants, the VGB monotherapy group (n = 9) included those taking VGB alone, and the off-VGB group (n = 7) included those who had discontinued VGB in the last 6 months., Methods: Scotopic flash, photopic flash, and 30-Hz flicker ERG results were recorded according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standard. The clinical electro-oculogram (EOG) results were recorded according to the ISCEV standard., Main Outcome Measures: Implicit time and amplitudes of the A- and B-waves of the flash and 30-Hz flicker ERGs were recorded. Summed amplitude of the first three oscillatory potential wavelets were recorded. The light-peak to-dark-trough Arden ratio of the EOG was evaluated., Results: Although photopic ERG B-wave reduction was most frequent in patients in the VGB multitherapy group (48% of eyes), a significant number of eyes in all three groups had scotopic ERG B-wave reduction. The 30-Hz flicker ERG result was abnormally reduced in all three groups. There was no significant difference in the frequency of occurrence in ERG result abnormalities between the VGB monotherapy and VGB multitherapy groups. The EOG results revealed reduced Arden ratios in all three groups; however, there was a significantly lower frequency of EOG abnormalities noted in the off-VGB group (P = 0. 0373). There was no statistically significant relationship between the frequency of electrodiagnostic abnormalities and the duration of use or the total cumulative dosage of Vigabatrin in any of the three groups., Conclusions: These findings of scotopic ERG result abnormalities suggest that VGB alone has an effect on inner electroretinal function at the level of the Müller cell. Concomitant EOG abnormalities suggest a substantial effect of VGB on outer retinal function that may be reversible after cessation of VGB treatment.

Objective: To investigate the potential toxicity to the retina of gentamicin injected near surgically thinned scleral areas in a rabbit model., Design: Experimental study., Methods: Scleral scraping to half thickness was performed in the superotemporal scleral area in both eyes of adult rabbits (n = 10). Gentamicin sulfate was injected subconjunctivally to the right eye and saline to the left eye, which always served as a control eye. Four weeks after the procedure, electroretinography (ERG) was performed to assess retinal function. Then, the eyes were enucleated and prepared for histologic evaluation of structural damage. In four eyes of two additional rabbits, vitreous gentamicin concentrations were measured using a fluorescence polarization assay., Main Outcome Measures: Dark- and light-adapted ERG responses and histopathologic damage., Results: Dark- and light-adapted ERG responses in all rabbits were similar in the experimental and control eyes. Gentamicin levels were more than 10 microg/ml after subconjunctival injection of gentamicin with scraping and 0.29 microg/ml after subconjunctival injection of gentamicin with no scraping. Histopathologic examination revealed significant local damage to the photoreceptors adjacent to the area of scraping and subconjunctival injection. A significantly lesser degree of damage was seen if gentamicin was injected in pigmented rabbits or in albino rabbits, but only 4 weeks after scleral scraping., Conclusions: Increased penetration of gentamicin through thinned sclera may lead to toxic levels of the drug in a localized area adjacent to the site of injection. These toxic effects are also influenced by the degree of pigmentation and acute inflammation.

The pathogenesis of the pattern reversal visual evoked potential (PRVEP) abnormalities in patients with Wilson's disease (WD) has not been investigated earlier. Since electroretinography (ERG) assesses the functional integrity of the retina, it was used along with PRVEP to localize the abnormalities in PRVEP in Wilson's patients. Ten newly diagnosed Wilson's disease patients underwent PRVEP and flash ERG soon after the diagnosis was established. The PRVEP latencies were prolonged in comparison with the controls (P<0.001). Photopic and scotopic A waves and oscillatory potentials were prolonged (P<0. 02) with reduction in amplitudes of photopic A and B waves (P<0.001). Six of these patients were subjected to repeat PRVEP and flash ERG after the clinical improvement with specific therapy. Comparison of the pre and post-treatment visual electrophysiological studies revealed significant reduction in latencies of PRVEP and flash ERG A wave (P<0.05) with increase in amplitudes of P100 of PRVEP (P<0.05), A and B waves of flash ERG (P<0.01). These findings confirm the reported PRVEP changes in WD and in addition demonstrate the reversibility of the retinal dysfunction which partially contributes to the PRVEP abnormalities. To the best of our knowledge this is the first study of ERG in patients with Wilson's disease in the literature. Further, there have been no earlier reports in the literature evaluating the effect of specific treatment on the PRVEP and ERG in Wilson's disease.

Purpose: The retinal dysfunction and the delayed visual cortex responses shown by patients affected by glaucoma can be objectively assessed by Pattern Electroretinogram (PERG) and Visual Evoked Potentials (VEP) recordings. The present study aims to evaluate the effects of nicergoline on the retinal function and on the visual cortical responses in glaucoma patients., Methods: Sixty patients (mean age 44.6+/-3.7) with open angle glaucoma were enrolled. The patients were divided into two groups: NG Group, where 30 patients were treated with nicergoline (Cebran((R)), 2 cps day) for 30 days; and CG Group, where 30 patients were not treated. Simultaneous recordings of PERG and VEP were performed in NG patients at the baseline, at 30 days after treatment with nicergoline (day 30), and at 45 days from the end of the treatment (day 75). PERG and VEP were recorded in CG patients at the baseline and after 30 and 75 days. The visual stimulus for recording PERGs and VEPs was a checkerboard whose elements subtended a visual arc of 60' and 15' with a 70% contrast, and alternated at a frequency of 2 Hz., Results: At the baseline none of the electrophysiological parameters observed in NG Group patients differed (P>0.05) from those of CG Group patients. At days 30 and 75, in CG Group patients the values of the PERG and VEP parameters were unmodified (P>0.05) with respect to the baseline. In NG Group patients, the 30-day treatment period with nicergoline induced a significant (P<0.01) improvement of the PERG and VEP parameters. At day 75 all the electrophysiological parameters of NG Group did not differ significantly (P>0.05) from those at the baseline., Conclusion: Treatment with nicergoline induces an improvement of the retinal function and of the visual cortical responses in patients affected by glaucoma. This effect disappears within 45 days after the suspension of the treatment., (Copyright 1999 Academic Press.)

Nicergoline is an ergot alkaloid derivative acting as a neuroprotective agent. In the present investigation, b-wave time-course recovery profiles under both light- and dark-adapted conditions, were studied in order to evaluate the possible effectiveness of nicergoline in the protection of the rabbit retina. Retinal ischaemia was induced by bilateral occlusion of common carotid artery in male rabbit of the Dutch strain. Groups of animals were subjected to 15-, 30- and 60-min periods of ischaemia under pentobarbital anaesthesia. Electroretinogram recordings were simultaneously obtained from both eyes, using, as the stimulus, the brightest flash from a stimulator positioned 15 cm in front of each eye. The treatment with nicergoline, administered immediately before the carotid occlusion, induced a significant protection only when the ischaemia seemed to cause retinal damage that the reperfusion alone was not able to recover completely. Nicergoline did not modify the recovery rate after 15-min or 30-min light-adapted and 15-min dark-adapted ischaemia; in these conditions the controls showed a full recovery. After 30-min dark-adapted ischaemia, the maximum recovery of the controls was 82%, and nicergoline significantly improved b-wave amplitude at all time points of reperfusion up to the complete recovery. Rabbit retina was irreversibly damaged by a 60-min ischaemia. In these conditions nicergoline significantly increased the percentage of b-wave recovery both in light- and dark-adapted ERG. Nicergoline, probably on the basis of its metabolic actions, seems to be effective in severe conditions of hypoxia and is more potent in dark than in light-adapted conditions. Its effectiveness in these experimental conditions could be justified by the different oxygen consumption of the photoreceptors in light and dark and the different sensitivity of cones and rods to the ischaemia.

Some hypotheses suggest that lithium produces its therapeutic effect by reducing sensitivity to light at the level of the retina. In humans, acute administration of lithium is associated with a reduction in retinal light sensitivity. To determine whether similar retinal light sensitivity changes occur with chronic use, we studied 24 euthymic bipolar patients on chronic lithium treatment and 21 age- and sex-matched normal comparison subjects using electroretinography (ERG) and electro-oculography (EOG). No significant differences were found in ERG b-wave amplitudes or implicit times, or in EOG ratios, between the two groups. We conclude that chronic lithium use is not associated with differences in retinal light sensitivity when bipolar patients are compared to normal comparison subjects, and that there is no evidence for retinal toxicity with long-term lithium treatment.

To clarify the chronic effect of lead exposure on the central and peripheral nervous systems (CNS and PNS), we performed neurophysiological tests on 41 lead-exposed male workers. Unexposed workers (controls, N = 39) were examined for auditory brain stem response (ABR), and their ABR parameters were compared with those of 15 lead-exposed workers age-matched to the controls. Neurophysiological tests included those of motor and sensory nerve conduction velocity of the radial nerve (MCV, SCVwa and SCVfw), electroretinograms, pattern reversal visual evoked potential (VEP), ABR, and short-latency somatosensory evoked potentials (SLSEP). Neurophysiological parameters were analyzed by regression analysis [independent parameters: age, exposure duration, and current and time-weighted average lead concentration in whole blood (PbB and TWA-PbB)]. ABR parameters were also tested by Student's t test. Significant negative correlations were found between radial MCV and TWA-PbB and SCVwa and PbB, while significant positive correlations were found between the latency of component N145 of VEP and exposure duration and between the latency of component N20 of SLSEP and PbB. The mean of interpeak latency between component III and V of ABR of 15 lead-exposed workers was significantly prolonged compared with that of the control group. These results suggested that lead exposure has a greater effect on the conduction function in the PNS than in that of the CNS in somatosensory and auditory pathways, and inversely in visual pathway.

In order to better understand the role of Calcitonin gene-related peptide (CGRP) in mammalian retina, the dose related effects of human CGRP (hCGRP) on rabbit electroretinogram (ERG) were examined in the present study. CGRP was administered intraocularly in doses of 0.1, 1.0 and 10.0 micrograms. ERG A- and B-wave as well as oscillatory potentials (P1, P2, P3 and P4) were recorded. The highest dose of CGRP (10.0 micrograms) significantly increased the amplitudes of the A-wave and OP components (P1, P2, P3 and P4) produced by relatively high stimulus intensity. The same dose of the peptide also enhanced B-wave amplitude at all intensities studied. The effects of the intermediate dose of CGRP (1.0 microgram) on the B-wave amplitudes were dependent on stimulus intensities. B-wave amplitudes at high stimulus intensities were not affected by 1.0 microgram of CGRP but were significantly increased with relatively lower stimulus intensities. The amplitudes of P3, one of OP components, were significantly increased. However, amplitudes of A-wave and other OP components (P1, P2 and P4) were not affected by 1.0 microgram CGRP. The lowest dose of the peptide (0.1 microgram) did not affect any amplitudes of ERG components. Implicit times of A-wave, B-wave and OP components were not significantly affected by the different doses of CGRP. Taken together, these results indicate that CGRP may play a functional role in modulating retinal responses to photic stimulation.

Background: At times, anesthesia is necessary to test children's electroretinographic (ERG) responses. Halothane, an anesthetic commonly used for pediatric patients, affects some aspects of ERG responses, but it is unknown if halothane affects ERG parameters evaluated by contemporary clinical protocols., Methods: Scotopic and photopic ERG responses were recorded from children when awake and then under halothane., Results: Halothane has no effect on scotopic b-wave stimulus/response parameters, including amplitude, sensitivity, and implicit time. Scotopic a-wave amplitudes, implicit times, model parameters, and ratio of a- to b-wave amplitudes are unaffected by halothane. The amplitudes and implicit times of photopic responses to red flashes and 30 Hz flickering white light are not altered by halothane. Halothane causes no significant change in amplitudes and implicit times of the oscillatory potential wavelets., Conclusion: These results suggest that significant departures of ERG responses (studied with the protocol described herein) from a laboratory's normal values cannot be attributed to halothane.