The effects of pharmacological accommodation and cycloplegia on axial length and choroidal thickness.

PURPOSE: To investigate the effects of pharmacological accommodation and cycloplegia on ocular measurements. METHODS: Thirty-three healthy subjects [mean (±SD) age, 32.97 (±5.21) years] volunteered to participate in the study. Measurement of the axial length, macular and choroidal thickness, refractive error, and corneal topography, as well as anterior segment imaging, were performed. After these procedures, pharmacological accommodation was induced by applying pilocarpine eye drops (pilocarpine hydrochloride 2%), and the measurements were repeated. The measurements were repeated again after full cycloplegia was induced using cyclopentolate eye drops (cyclopentolate hydrochloride 1%). The correlations between the measurements were evaluated. RESULTS: A significant increase in subfoveal choroidal thickness after applying 2% pilocarpine was identified (without the drops, 319.36 ± 90.08 µm; with pilocarpine instillation, 341.60 ± 99.19 µm; with cyclopentolate instillation, 318.36 ± 103.0 µm; p<0.001). A significant increase in the axial length was also detected (without the drops, 23.26 ± 0.83 mm; with pilocarpine instillation, 23.29 ± 0.84 mm; with cyclopentolate instillation, 23.27 ± 0.84 mm; p=0.003). Comparing pharmacological accommodation and cycloplegia revealed a significant difference in central macular thickness (with pilocarpine instillation, 262.27 ± 19.34 µm; with cyclopentolate instillation, 265.93 ± 17.91 µm; p=0.016). Pilocarpine-related miosis (p<0.001) and myopic shift (p<0.001) were more severe in blue eyes vs. brown eyes. CONCLUSION: Pharmacological accommodation may change ocular measurements, such as choroidal thickness and axial length. This condition should be considered when performing ocular measurements, such as intraocular lens power calculations.

Topiramate-Induced Changes in Anterior Chamber Angle and Choroidal Thickness.

PURPOSE: To investigate the acute effects of topiramate on the anterior chamber angle (ACA) and choroidal thickness in patients with migraine. METHODS: This prospective study included 15 eyes of 15 patients with migraine who have been scheduled to start topiramate therapy. All patients underwent complete ophthalmic examination including measurement of the ACA and choroidal thickness using a spectral domain optical coherence tomography device (Optovue Inc.) and refractive status evaluation with an autorefractokeratometer (KR-8100; Topcon) at the baseline and 1 week after starting therapy. The patients were asked to report any pain or discomfort in their eyes during therapy at the follow-up visit. RESULTS: None of the patients experienced pain or discomfort in their eyes. The mean ACA significantly decreased at the first week of the therapy compared with the baseline levels (40.34±7.06° and 36.89±6.87°, respectively) (P=0.001). However, the mean choroidal thickness increased from 277.33±95.60 µm at the baseline to 323.40±84.50 µm at the first week (P=0.01). There was a nonsignificant increase in the mean refractive error (from -0.25±0.54 diopter [D] at the baseline to -0.38±0.49 D after 1 week) (P=0.06). CONCLUSIONS: Topiramate can acutely decrease the ACA and increase the choroidal thickness. Because these effects may be asymptomatic, patients with migraine who start this therapy should be warned to be closely followed up by an ophthalmologist.

Ketamine-xylazine anesthesia causes hyperopic refractive shift in mice.

Mice have increasingly been used as a model for studies of myopia. The key to successful use of mice for myopia research is the ability to obtain accurate measurements of refractive status of their eyes. In order to obtain accurate measurements of refractive errors in mice, the refraction needs to be performed along the optical axis of the eye. This represents a particular challenge, because mice are very difficult to immobilize. Recently, ketamine-xylazine anesthesia has been used to immobilize mice before measuring refractive errors, in combination with tropicamide ophthalmic solution to induce mydriasis. Although these drugs have increasingly been used while refracting mice, their effects on the refractive state of the mouse eye have not yet been investigated. Therefore, we have analyzed the effects of tropicamide eye drops and ketamine-xylazine anesthesia on refraction in P40 C57BL/6J mice. We have also explored two alternative methods to immobilize mice, i.e. the use of a restraining platform and pentobarbital anesthesia. We found that tropicamide caused a very small, but statistically significant, hyperopic shift in refraction. Pentobarbital did not have any substantial effect on refractive status, whereas ketamine-xylazine caused a large and highly significant hyperopic shift in refraction. We also found that the use of a restraining platform represents good alternative for immobilization of mice prior to refraction. Thus, our data suggest that ketamine-xylazine anesthesia should be avoided in studies of refractive development in mice and underscore the importance of providing appropriate experimental conditions when measuring refractive errors in mice.

Comparison of two artificial tear formulations using aberrometry.

BACKGROUND: This study investigates the effect of artificial tears of different viscosities on aberrations of healthy eyes. METHODS: We recruited subjects from the student population of the Northeastern State University Oklahoma College of Optometry. Using the Complete Ophthalmic Analysis System (COAS), aberrometry measurements were taken every second for 60 seconds with a blink every 10 seconds. We made measurements of the naked eye, then after instillation of TheraTears non-preserved drops, and after instillation of SystanePF, a more viscous formulation. Zernike coefficients up to the sixth order were recorded and analysed. We evaluated changes in spherical and astigmatic dioptric powers and coma-like, spherical aberration-like and total higher-order aberration (HOA) RMS values as a function of time. RESULTS: Both drops yielded significantly higher values than the naked eye for HOA RMS and cylindrical power as well as a hyperopic shift in spherical equivalent (p < 0.001,paired t-test). SystanePF, the more viscous tear, showed significantly higher values than TheraTears in HOA RMS and cylinder in all inter-blink periods (p < 0.001, paired t-test). CONCLUSIONS: This study shows artificial tears can have a measurable and significant impact on aberrations of healthy eyes. This effect is sustained for at least one minute and its magnitude appears to be related to the viscosity of the tear formulation.

[The influence of phenylephrine and tropicamide on higher order monochromatic aberrations]. / Einfluss von Phenylephrin und Tropicamid auf Aberrationen höherer Ordnung.

BACKGROUND: For wave-front guided corneal surgery, measuring higher order monochromatic aberrations in mydriasis is needed. However, a potential influence of mydriatic drugs on such aberrations could distort the ablation profile. METHOD: Wave-front analysis was carried out on 20 (tropicamide) and 19 (phenylephrine) eyes after dark adaptation, followed by measurement after the instillation of the mydriatics one after another. RESULTS: Phenylephrine had no significant influence on the wave-front; neither sphere nor RMS data differed from those taken after dark adaptation. After instilling tropicamide, significant changes in Z(2) (0) and, in parallel, also of the sphere were found. The RMS showed no significant difference, only the spherical aberration Z(4) (0) was reduced by an average of 0.035 microm. CONCLUSION: The wave-front changes individually through the mydriasis due to phenylephrine and tropicamide. In the case of tropicamide, the deviation is statistically significant. Therefore, abandonment of these mydriatics before refractive surgery can be recommended, as can the use physiological pupil dilatation. Because of its lower influence, phenylephrine should be the first choice if dimout effects no adequate mydriasis.

Vision abnormalities in young children exposed prenatally to organic solvents.

Despite an accumulating body of evidence demonstrating that the visual system is an important target for organic solvent toxicity in adults, little attention has been paid to the visual functioning of children with prenatal exposure to organic solvents. The present study aimed to: (1) determine prospectively whether prenatal solvent exposure increases the risk of visual deficits in infants and (2) assess the relationship between estimates of exposure level and integrity of visual responses. A sample of 21 infants born to women who were occupationally exposed to solvents during pregnancy was compared with 27 non-exposed age-matched control infants. All mothers were recruited from Motherisk, an antenatal counseling service in Toronto, Canada. Contrast sensitivity and grating acuity were assessed using a sweep visual evoked potential (VEP) technique whereas chromatic- and achromatic mechanisms were assessed using a transient VEP technique. Exposure level was estimated from questionnaire data obtained during pregnancy. Testers were masked to exposure status. Results showed a significant reduction in contrast sensitivity in the low and intermediate spatial frequency range in solvent-exposed infants compared to controls (p<0.001). With respect to grating acuity, there was a significant effect of exposure level, with children in the high exposed having reduced grating acuity compared with children in the low exposed group (p<0.025) and controls (p=0.02). Regarding color vision, 26.3% of infants in the exposed group versus 0% of the controls produced abnormal VEP responses to the red-green onset stimulus (p<0.01), but not to either blue-yellow or achromatic stimuli. No differences were found with respect to latency or amplitude of chromatic and achromatic response. These findings suggest that prenatal solvent exposure is associated with selective visual deficits, including reduced contrast sensitivity and abnormal red-green vision. Increasing levels of exposure may lead to further visual deficits affecting grating acuity. These findings support the need for a re-evaluation of current occupational exposure standards for pregnant women.

Ophthalmic findings in fetal anticonvulsant syndrome(s).

PURPOSE: To report the prevalence of ocular abnormalities in a group of children diagnosed with fetal anticonvulsant (FAC) syndrome(s). DESIGN: Retrospective, observational, noncomparative case series. PARTICIPANTS: Forty-six children, age range 8 months to 16 years 5 months (mean, 7 years 1 month), with a confirmed diagnosis of an FAC syndrome. Thirty-seven subjects were exposed in utero to sodium valproate (29 as monotherapy), and the remainder (n = 9) to other anticonvulsants, mainly carbamazepine. METHODS: A total of 46 subjects underwent ophthalmic assessment consisting of visual acuity, cover test, ocular movements, analysis of spectacle lens power, cycloplegic refraction, and anterior segment examination with portable slit lamp, plus direct and indirect ophthalmoscopy. MAIN OUTCOME MEASURES: Refraction and ocular motility status. RESULTS: Thirty-one of 46 (67%) had ocular abnormalities, most commonly errors of refraction (19 of 46; 41%). Myopia was common (14 of 28; 50%) in those exposed to valproate monotherapy and there were high frequencies of strabismus (20%), astigmatism (24%), and anisometropia (11%) in the group as a whole. Thirty-one percent of myopes and 27% of astigmates did not wear glasses, of whom three subjects and two subjects, respectively, were less than 8 years old and therefore at risk of anisometropic or ametropic amblyopia. One subject had epicanthus, one color vision deficiency, and one bilateral congenital cataract. CONCLUSIONS: We conclude that (1) abnormal ophthalmic findings are common in subjects with confirmed FAC syndrome, in particular myopia in those with fetal valproate syndrome; (2) children with FAC syndrome should receive preschool vision testing; (3) preschool vision testing should be considered in all children exposed to anticonvulsants in utero.

Evidence for a potential role of glucagon during eye growth regulation in chicks.

Eye growth and refraction are regulated by visual processing in the retina. Until now, the messengers released by the retina to induce these changes are largely unknown. Previously, it was found that glucagon amacrine cells respond to defocus in the retinal image and even to its sign. The expression of the immediate-early gene product ZENK increased in this cell population in eyes wearing plus lenses and decreased in minus lens-treated chicks. Moreover, it was shown that the amount of retinal glucagon mRNA increased during treatment with positive lenses. Therefore, it seems likely that these cells contribute to the visual regulation of ocular growth and that glucagon may act as a stop signal for eye growth. The purpose of the present study was to accumulate further evidence for a role of glucagon in the visual control of eye growth. Chicks were treated with plus and minus lenses after injection of different amounts of the glucagon antagonist des-His1-Glu1-glucagon-amide or the agonist Lys17,18,Glu21-glucagon, respectively. Refractive development and eye growth were recorded by automated infrared photorefraction and A-scan ultrasound, respectively. The glucagon antagonist inhibited hyperopia development, albeit only in a narrow concentration range, and at most by 50%, but not myopia development. In contrast, the agonist inhibited myopia development in a dose-dependent fashion. At high concentrations, it also prevented hyperopia development. The amount of glucagon peptide in the retinae and choroids of lens-treated chicks and its diurnal variation was measured by using a radio-immunoassay. Retinal glucagon content decreased after minus lens treatment and choroidal glucagon content increased after plus lens treatment. No diurnal variation in the retinal amount of glucagon was detected. In addition, using an optokinetic nystagmus paradigm, the effect of glucagon and the antagonist des-His1-Glu9-glucagon-amide on suprathreshold contrast sensitivity was studied. Glucagon reduced contrast sensitivity (which might be linked to a signal for growth inhibition) whereas the antagonist des-His1-Glu9-glucagon-amide increased contrast sensitivity. The results of the study are in line with the hypothesis that glucagon plays a role in the visual control of eye growth in the chick.

Refractive change after dorzolamide use in patients with primary open-angle glaucoma and ocular hypertension.

The purpose of this study was to evaluate refractive and anterior chamber depth changes after short-term dorzolamide use in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study was prospective and non-comparative and included 34 patients. Baseline refraction and anterior chamber depth were compared to the refraction and anterior chamber depth 14 days after commencing dorzolamide to determine if refraction or anterior chamber depth had been affected. Before dorzolamide use, the mean refractive error was -0.88 +/- 3.53 D (+/-SD). The mean refractive error was -0.94 +/- 3.65 D (+/-SD) two hours post-dose after 14 days of dorzolamide use, which was not significantly different (P = 0.50). The mean pre-treatment anterior chamber depth was 3.088 +/- 0.385 mm (+/-SD), which did not differ significantly from the post-treatment anterior chamber depth mean of 3.092 +/- 0.389 mm (+/-SD) (P = 0.88). The results of the study show that refraction and anterior chamber depth are not significantly altered by short-term dorzolamide use in patients with POAG and OH with no history of previous dorzolamide use.

Irreversible corneal decompensation in patients treated with topical dorzolamide.

PURPOSE: To describe irreversible corneal decompensation after topical dorzolamide hydrochloride (Trusopt; Merck and Co, Inc, West Point, Pennsylvania) therapy in nine patients who had histories consistent with corneal endothelial compromise. METHOD: Multicenter review of patients' charts. RESULTS: Nine eyes of nine patients developed overt corneal decompensation after starting topical dorzolamide, a condition that did not resolve with drug cessation. This occurred after 3 to 20 weeks (mean, 7.8) of therapy. All nine patients had undergone intraocular surgery. Eight patients had undergone cataract surgery; three were aphakic and three had posterior chamber intraocular lenses. Two patients had anterior chamber intraocular lenses and also had undergone trabeculectomies. Four patients had undergone penetrating keratoplasties, each case complicated by episodes of corneal allograft rejection that were successfully treated. Two patients had asymptomatic Fuchs endothelial dystrophy. Seven patients have since undergone successful penetrating keratoplasties. CONCLUSION: The reports suggest that dorzolamide can cause irreversible corneal edema in a subset of glaucoma patients with endothelial compromise. The findings suggest a rationale for research into the long-term effects of dorzolamide on the corneal endothelium.

Visual anomalies in young children exposed to cocaine.

PURPOSE: The number of children exposed to cocaine in utero each year is increasing. Recent reports suggest significant visual anomalies in infants prenatally exposed to cocaine. The purpose of this retrospective study was to determine if children exposed prenatally to cocaine were at a greater risk for visual abnormalities, such as strabismus and significant refractive errors. METHODS: This pilot study was conducted at two sites, an outpatient clinic and a hospital-based practice. Consecutive files from January to July, 1993, of 79 children (aged 4 months to 94 months); who were identified by case history or meconium analysis information as being exposed to cocaine in utero, were reviewed. Fifty-five children met the inclusion criteria for the study. In addition, a control group of 100 pediatric patients were randomly selected from the pediatric patients seen at the outpatient clinical site. RESULTS: Of the 30 children from the Illinois Eye Institute (IEI) and the 25 children from The Children's Hospital (TCH), spherical refractive errors in the right eye ranged from +6.50 to -12.50 D. The median refractive errors were +0.75 and +0.50 D, respectively. No statistical difference was found in spherical refractive error, astigmatism, or anisometropia between the cocaine-exposed cohorts and the control group (N = 100). Strabismus was found in 15/55 (27%) of the children in the cocaine-exposed group. There was a statistically significant difference in the prevalence of strabismus between the cocaine-exposed group and the control group. Further analysis revealed that full birthweight (> 2500 g) children prenatally exposed to cocaine were at a greater risk for strabismus as compared to the full birthweight control group. Ocular abnormalities were rare, but included optic nerve atrophy and retinopathy of prematurity. CONCLUSIONS: These data suggest cocaine exposure during pregnancy may place a child at risk for conditions that may negatively impact the visual system, specifically strabismus.

Ocular symptoms and signs associated with suramin sodium treatment for metastatic cancer of the prostate.

PURPOSE: Therapy with suramin sodium has been associated with photophobia, iritis, optic atrophy, and vortex keratopathy. We studied the ocular findings in patients who underwent treatment with suramin sodium for metastatic cancer of the prostate. METHODS: In a prospective study, 114 patients who underwent treatment with suramin sodium for cancer of the prostate had an ophthalmologic examination with two weeks of onset of treatment and two weeks after termination of therapy. Additional examinations were performed on patients who developed ocular symptoms during suramin sodium therapy. RESULTS: Nineteen (16.6%) of 114 patients developed ocular symptoms and signs while taking suramin sodium. Thirteen of these patients developed bilateral corneal epithelial whorllike deposits. In ten patients, the corneal deposits were associated with foreign body sensation and lacrimation. Symptoms in all of these patients resolved with topical lubricants. Three patients developed asymptomatic corneal deposits. Seven patients had blurred vision and were found to have a mean hyperopic shift in refractive error of 1.13 +/- 0.45 diopters (range, 0.75 to 2.00 diopters) that persisted throughout their treatment course. None of these patients had a decrease in best-corrected visual acuity. CONCLUSIONS: In this study, ocular symptoms and signs associated with suramin sodium were common but were not considered a dose-limiting toxicity. Hyperopic shift in refractive error is a previously unreported ocular finding in association with suramin sodium therapy.

ERG of form deprivation myopia and drug induced ametropia in chicks.

Chick eyes occluded for various periods or treated with various concentrations of kainic acid (KA) or 2-amino-4-phosphonobutylate (APB) during development showed characteristic changes of electroretinography and of refraction. In occluded eyes, oscillatory potential amplitudes (OP-A) were reduced, even with high-intensity stimulation, in proportion to duration of occlusion, but b wave amplitude was unchanged, implying functional changes in inner layers of the deprived retina. OP-A reduction after only 1 week of occlusion and reversibility of this change might reflect retinal changes preceding axial elongation. KA was confirmed to induce myopia with axial elongation and APB to induce hyperopia with axial shortening. KA and APB both suppressed OP-A. KA reduced ON and OFF responses, but low-dose APB suppressed only ON responses. Study results suggest that myopia could be induced by changes of inner retina mediating OP attenuation and degradation of ON and OFF responses. This manuscript reports unpublished work that is not currently under consideration for publication elsewhere.

High dose steroids in acute relapses of multiple sclerosis: MRI evidence for a possible mechanism of therapeutic effect.

The integrity of the blood-brain barrier (BBB) in multiple sclerosis (MS) was monitored by serial gadolinium-(Gd)-DTPA enhanced MRI during and after the treatment of acute relapses with a three day course of high dose intravenous methylprednisolone (IVMP). During treatment there was a rapid reduction of BBB abnormalities in 96% of enhancing lesions. In spite of sustained clinical improvement, many lesions re-enhanced within a few days of stopping IVMP, and new lesions frequently appeared within one month. It is possible that the rapid, albeit transient, reversal of BBB abnormalities contributes to the accelerated recovery from relapses associated with IVMP treatment.

Refractive-error changes in kitten eyes produced by chronic on-channel blockade.

The dependence of the emmetropization process on retinal ON-channel activity was examined in developing kittens by making regular intravitreal injections of D,L-2-amino-4-phosphonobutyric acid (APB). In comparison to sham-injected control eyes, the APB-treated eyes had shorter axial lengths and were more hyperopic. Since chronic atropinization did not alter the development of the APB-induced hyperopia, these anomalous refractive errors are not the result of altered accommodative function. The axial hyperopia observed in the APB-treated eyes indicates that the mechanisms responsible for normal axial elongation are dependent to some extent on ON-channel activity and that, even in the presence of a clear retinal image, OFF-channel activity, by itself, is not sufficient to regulate the normal emmetropization process.

Kainic acid-induced eye enlargement in chickens: differential effects on anterior and posterior segments.

Intravitreal injections of kainic acid were used to examine the significance of normal retinal activity for eye growth in chickens, this acid being chosen because of its known, selective neurotoxic effects on cells in the chicken retina. A 6 nmole dose of kainic significantly reduces amacrine cell numbers when used in very young chickens, while higher doses of kainic acid also affect bipolar and horizontal cell numbers. The effects of intravitreal injection of kainic acid on eye growth were assessed 4 weeks after treatment. A 200 nmole dose of kainic acid, used with day-old and 14-day-old chickens, had opposing effects on the anterior and posterior segments of the eye; while growth of the anterior segment was inhibited, the posterior segment was enlarged, predominantly in the equatorial direction. A 20 nmole dose of this acid similarly affected growth in 14-day-old chickens, but in day-old chickens, the anterior segment was also enlarged and the overall eye enlargement had an axial bias. Myopia was the most common refractive error associated with both patterns of development. A 2 nmole dose of kainic acid was without effect on eye growth. Parallels are drawn between these eye enlargement phenomena and those described in chickens whose visual environments have been manipulated. Our results indicate that normal retinal activity is fundamental to normal eye growth in chickens, and furthermore, that growth of the anterior and posterior segments of the chicken eye are independently regulated.