A detailed paraxial schematic eye for the White Leghorn chick

We studied the normal ocular development of the chick (Gallus gallus domesticus, White Leghorn) up to 15 days of age using both longitudinal and cross-sectional methods. The change in refractive error, corneal curvature and axial ocular distances were used to construct schematic eyes. Equations are presented which allow prediction of refractive error changes associated with changes in vitreous chamber depth. The mean refractive error was +3.2 D at hatching, which reduced by 66% over the first 3 days and stabilized by 11 days of age. The lens thickened and the anterior chamber deepened from hatching, but vitreal elongation and corneal flattening were delayed until after the first 3 days, suggesting that normal eye growth may be initially inhibited or inactive during an initial emmetropization period, and subsequently activated in response to myopic defocus arising from the continually expanding lens. Finally, when compared with published data on other chick strains, we find differences in the degree of hyperopia at hatching due to differences in lens thickness. However, the rate of ocular and vitreal expansion and the developmental changes in corneal power are similar, making the schematic eyes presented here generally applicable to different strains of chickens.     

Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in Monozygotic and Dizygotic Twin Pairs

BackgroundThe similar genetic background of a pair of twins, and the similar environmental impacts to which they are exposed allow an exact and objective investigation of various constitutional and environmental factors in naevus development. As far as we are aware, this is the first published survey that simultaneously examines cutaneous and ocular pigmented lesions in an appreciable sample of identical and non-identical twins.Methods172 pairs of twins of Caucasian origin were included in this study. A whole-body skin examination and a detailed ophthalmological examination were performed to determine the density of melanocytic lesions. A standardized questionnaire was used to assess the data relating to constitutional, sun exposure and other variables.ResultsA notably high proportion of the subjects (36.78%) manifested one or more clinically atypical melanocytic naevi (CAMNs), and approximately one-third (31.4%) of them at least one benign uveal pigmented lesion (BUPL). The incidence of iris freckles (IFs), iris naevi (INs) and choroidal naevi (CHNs) proved to be 25.35%, 5.98% and 3.52%, respectively. The interclass correlation coefficients for common melanocytic naevi (CMNs), CAMNs, and INs were 0.77, 0.76 and 0.86 in monozygotic twins, as compared with 0.5, 0.27 and 0.25 in dizygotic twin pairs, respectively. A statistically significant correlation was found between the prevalence of CAMNs and that of INs.ConclusionsThis significant correlation suggests the existence of a subgroup of Caucasian people with an increased susceptibility to both cutaneous and ocular naevus formation. There is accumulating evidence that, besides the presence of cutaneous atypical naevi, INs can serve as a marker of a predisposed phenotype at risk of uveal melanoma. The correlation between cutaneous and ocular pigmented lesions underlines the need for the adequate ophthalmological screening of subjects with CAMNs and INs.     

On emmetropization

The growth of the ocular elements, such as axial length, corneal power, and lens power, is represented by a set of first order, linear, coupled differential equations. Since the rate of growth and the size of the ocular elements vary from one individual to the next, the parameters which arise in these differential equations are assumed to be Gaussian random variables. These assumptions provide a basis for understanding the controlled growth of the eye. They predict that the distribution of refractive error is normal at birth and leptokurtic in adulthood. They also predict that the variance of refractive error will decrease with age provided the second order moments of the random variables obey some rather general conditions.     

Association between Childhood Strabismus and Refractive Error in Chinese Preschool Children

PurposeTo investigate the association between concomitant esotropia or concomitant exotropia and refractive error in preschool childrenMethodsA population-based sample of 5831 children aged 3 to 6 years was selected from all kindergartens in a representative county (Yuhuatai District, Nanjing, Jiangsu Province) of Nanjing, China. Clinical examinations including ocular alignment, ocular motility, visual acuity, optometry, stereopsis screening, slit lamp examination and fundus examination were performed by trained ophthalmologists and optometrists. Odd ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the association of refractive error with concomitant esotropia and concomitant exotropia.ResultsIn multivariate logistic regression analysis, concomitant esotropia was associated independently with spherical equivalent anisometropia (OR, 3.15 for 0.50 to <1.00 diopter (D) of anisometropia, and 7.41 for > = 1.00 D of anisometropia) and hyperopia. There was a severity-dependent association of hyperopia with the development of concomitant esotropia, with ORs increasing from 9.3 for 2.00 to <3.00 D of hyperopia, to 180.82 for > = 5.00 D of hyperopia. Concomitant exotropia was associated with astigmatism (OR, 3.56 for 0.50 to 1.00 D of astigmatism, and 1.9 for <0.00 D of astigmatism), myopia (OR, 40.54 for -1.00 to <0.00 D of myopia, and 18.93 for <-1.00 D of myopia), and hyperopia (OR, 67.78 for 1.00 to <2.00 D of hyperopia, 23.13 for 2.00 to <3.00 D of hyperopia, 25.57 for 3.00 to <4.00 D of hyperopia, and 8.36 for 4.00 to <5.00 D of hyperopia).ConclusionsThis study highlights the close associations between refractive error and the prevalence of concomitant esotropia and concomitant exotropia, which should be considered when managing childhood refractive error.     

Spontaneous ophthalmic lesions in young Swiss mice.

BACKGROUND AND PURPOSE: Outbred mice are frequently used in toxicity evaluation. Due to their small size, ophthalmologic examination of such animals is difficult with regard to restraint and use of instruments designed for human medicine. The clinical appearance and incidence of spontaneous ophthalmic lesions should be helpful in selecting mice for toxicity studies and allow distinction between intercurrent spontaneous ocular changes and those attributable to drugs or chemicals. METHODS: Pretest ophthalmologic examinations of about 3,000 4- to 5-week-old Swiss mice, Crl:CD1 (ICR)BR, conducted in 1995 and 1996, provided information about spontaneous ocular changes and their incidence. Eye evaluations were performed after pupil dilatation (0.5% tropicamide instillation), using indirect ophthalmoscopy, and when indicated, a portable slit lamp. RESULTS: Lenticular opacities and heterogeneity/prominence were the most common findings (up to 19%) in the anterior segment. Abnormalities of the cornea and iris were detected in up to 4% of mice. Hyaloid artery remnant, as well as isolated cases of floating bodies or hemorrhage, was observed in the vitreous of 12 to 17% of mice. Approximately 2 to 4% of mice had colobomatous fundus, retinal fold, or retinal atrophy. A few mice had chorioretinal atrophy, hemorrhage, or abnormal pattern of the retinal vasculature. Remaining findings consisted of incomplete palpebral fissure, microphthalmia, exophthalmia, ophthalmic hemorrhage, and scleral mass. CONCLUSIONS: Due to severity of the condition or interference with ocular examination, affected mice should be eliminated from experimental studies. Hence, pretest ocular examinations of mice are indicated in safety-assessment toxicity studies.     

Inferior ectopic pupil and typical ocular coloboma in RCS rats

Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F(1) rats nor N(2) (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma.     

A unifying theory of refractive error development

While retinal defocus is believed to be myopigenic in nature, the underlying mechanism has remained elusive. We recently constructed a theory of refractive error development to investigate its fundamental properties. Our Incremental Retinal-Defocus Theory is based on the principle that the change in retinal-defocus magnitude during an increment of genetically-programmed ocular growth provides the requisite sign for the appropriate alteration in subsequent environmentally-induced ocular growth. This theory was tested under five experimental conditions: lenses, diffusers, occlusion, crystalline lens removal, and prolonged nearwork. Predictions of the theory were consistent with previous animal and human experimental findings. In addition, simulations using a MATLAB/SIMULINK model supported our theory by demonstrating quantitatively the appropriate directional changes in ocular growth rate. Thus, our Incremental Retinal-Defocus Theory provides a simple and logical unifying concept underlying the mechanism for the development of refractive error.     

Usefulness of ophthalmic examination in postnatal observation in teratology studies.

Pregnant rats were irradiated with soft x-ray at a dose of 635 r or 1270 r on Day 9 or 11 of gestation. The eyes of F1 offspring were examined by indirect ophthalmoscopy and slit lamp biomicroscopy in postnatal weeks 3 to 7. Ophthalmoscopic examination of offspring irradiated at a dose of 635r or 1270r on Gestational Day 9 revealed iris and choroidal coloboma together with microphthalmia and anophthalmia at Postnatal Week 3 or later. Choroidal coloboma, an anomaly that cannot be detected by the common external observation method, was found ophthalmoscopically in one rat without any external ocular abnormalities. This fact suggests that ophthalmoscopy in postnatal observation can be useful to detect ocular teratogenic potential of test compounds in preclinical safety studies.     

Association between Ocular Sensory Dominance and Refractive Error Asymmetry

Purpose

To investigate the association between ocular sensory dominance and interocular refractive error difference (IRED).

Methods

A total of 219 subjects were recruited. The refractive errors were determined by objective refraction with a fixation target located 6 meters away. 176 subjects were myopic, with 83 being anisometropic (IRED ≥ 0.75 D). 43 subjects were hyperopic, with 22 being anisometropic. Sensory dominance was measured with a continuous flashing technique with the tested eye viewing a Gabor increasing in contrast and the fellow eye viewing a Mondrian noise decreasing in contrast. The log ratio of Mondrian to Gabor’s contrasts was recorded when a subject just detected the tilting direction of the Gabor during each trial. T-test was used to compare the 50 values collected from each eye, and the t-value was used as a subject’s ocular dominance index (ODI) to quantify the degree of ocular dominance. A subject with ODI ≥ 2 (p < 0.05) had clear dominance and the eye with larger mean ratio was the dominant one. Otherwise, a subject had an unclear dominance.

Results

The anisometropic subjects had stronger ocular dominance in comparison to non-anisometropic subjects (rank-sum test, p < 0.01 for both myopic and hyperopic subjects). In anisometropic subjects with clear dominance, the amplitude of the anisometropia was correlated with ODI values (R = 0.42, p < 0.01 in myopic anisometropic subjects; R = 0.62, p < 0.01 in hyperopic anisometropic subjects). Moreover, the dominant eyes were more myopic in myopic anisometropic subjects (sign-test, p < 0.05) and less hyperopic in hyperopic anisometropic subjects (sign-test, p < 0.05).

Conclusion

The degree of ocular sensory dominance is associated with interocular refractive error difference.     

A simple and accurate method for the measurement of the growth of cell monolayers

Summary A procedure has been developed for the accurate, quick, and simple indexing of the growth of insect cell monolayers with a reticule in the eyepiece of an inverted phasecontrast microscope. A magnification of ×500 is desirable for accuracy and ease of counting. Cell nuclei whose circumferences include any of the 25 points in the reticule are enumerated in each microscopic field. Counts of as few as five fields gave an error of 18.8% per flask. Ten fields gave an error of 11.5% and provided a sufficiently accurate comparison for many purposes. Forty counts allowed the measurement of differences between treatments with an error of 5.85%. A large number of treatments can be handled simultaneously, due to the small number of replicates necessary and the small amount of time required per treatment. When the capacity of different batches of lactalbumin hydrolysate to support growth was tested in our insect tissue culture medium, some of them were found to be suitable and others unsuitable. Doubling time of cell populations was measured, after the ratio of the average area of the nuclei at time 0 to that at timeX was used to multiply the number of nuclei counted at timeX. Average nuclear areas were satisfactorily measured by simple measurements of nuclear diameter on an ocular micrometer. The cell nuclei tended to decrease in area when cell monolayers reached confluence or became crowded. The number of replicates required was reduced, because the same flask could be used several times without disturbing the cell monolayer. The method of counting nuclei in a monolayer by means of reticule points and a phase-contrast microscope can also be adapted to the estimation of the absolute number of cells growing on the bottom of a flask. Portion of a thesis by the senior author submitted for the Ph.D. degree to the Graduate College of the University of Illinois. This research was supported in part by grant GB 20915 from the National Science Foundation and United States Public Health Service grant AI 6392 from the National Institutes of Health.     

Ophtalmoscopic examination in critically ill non-neutropenic patients: Candida endophtalmitis

Invasive Candida (IC) infection is the most common cause of endogenous endophthalmitis. Ocular candidiasis develops within three days and at least two weeks of fungemia. There are two characteristic ocular signs: Candida chorioretinitis defined as retina and choroid lesions without vitreal involvement, and Candida endophthalmitis defined as chorioretinitis with extension into the vitreous with characteristic fluffy balls. The most common initial visual symptoms are blurred vision and floaters. Amphotericin B, fluconazole and voriconazole are effective in the treatment of chorioretinitis; however, when vitreous is involved vitrectomy seems necessary. Early antifungal systemic treatment at first evidence of infection in patients at risk of IC, appears to decrease dramatically the incidence of endogenous fungal endophthalmitis, probably healing minimal chorioretinal infections. Routine ophthalmoscopic examination seems of little value in patients with positive blood culture, with early implementation of antifungal treatment, without symptoms of ocular infection and without impairment of the level of consciousness during the episode. However, periodic ophthalmoscopic examination should be performed in children with candidemia and critically ill patients with documented deep Candida infection.     

Physical and morphological aspects of the eye of the manatee trichechus inunguis natterer 1883: (Sirenia: Mammalia)

The eyes and aspects of vision of the Amazonian manatee Trichechus inunguis NATTERER 1883: (Sirenia: mammalia) have been examined in five animals, in relation to previous findings for sirenians. This paper presents a review of previous findings confirming those upon gross ocular anatomy, retinal histology and ocular refraction. The confirmation of a primarily rod retina, high receptor: ganglion cell ratio and low refractive error under water were of note. A visual pigment based upon vitamin A₁ and a difference spectrum of λ max at 505 nm was in agreement with Dartnalls nomogram. The findings suggest a retina more suited to low light levels and at best, moderate visual acuity, though motion perception appears present and a low degree of binocular vision possible.     

Simultaneous quantification of cefotaxime, desacetylcefotaxime, ofloxacine and ciprofloxacine in ocular aqueous humor and in plasma by high-performance liquid chromatography

Cefotaxime, given intravenously, is currently used as a broad-spectrum antibiotic for prophylaxis of intra- and postoperative infections in ocular lens surgery. A proposed therapeutic and economic alternative is the use of orally active fluoroquinolone ofloxacine as prophylactic agent. A HPLC method was developed for determination of both antibiotics in ocular aqueous humor and plasma in order to optimize dosage for safe surpassing minimal inhibitory concentration in the humor compartment. For plasma determinations a solid-phase extraction procedure was used with ciprofloxacine as internal standard. Detection limits for direct HPLC-analysis of ocular aqueous humor was 0.08 μg/ml for all compounds, whereas in plasma 0.31 μg/ml could be determined after solid-phase extraction.     

Effect of chronic exposure to welding light on Calabar welders.

It was generally observed that welders in Calabar, Nigeria did not always wear their protective goggles during welding. Since chronic exposure to welding light can impair vision this study was done to assess the effect of exposure to welding light on ocular function of welders in Calabar, Nigeria. There were 195 subjects comprising 110 welders (test) and 85 control subjects. Both groups were all male and had similar age range. The tests employed were clinical examination for ocular disorders, assessment of visual acuity, and opthalmoscopy. Test questionnaire was also used to record information on length of service, precautionary measures at work place, age and past ocular illnesses. The study also compared incidence of ocular disorders between the two groups of welders (arc and carbide welders). The mean ages of the welders and their control were not significantly different (27.53 +/- 10.0 vs 27.78 +/- 8.5 yrs respectively). There was a significantly [P < 0.01] higher incidence of pingueculum, cataract, allergic conjunctivitis, corneal opacity, and keratoconjunctivitis (arc eye) in welders than in their control subjects. However, visual acuity, incidence of pterygium and glaucoma were similar. Between the two groups of welders, the incidence of pterygium, corneal opacity and keratoconjunctivitis was significantly [P < 0.01] higher in arc welders than carbide welders. The incidence of pingueculum and glaucoma were however, similar. In conclusion, chronic exposure to welding light without adequate precaution may cause ocular disorders. Arc welding is more dangerous to ocular function than carbide welding. Length of service and age are predisposing factors to ocular disorders in the welding business.     

Retinal detachment following hockey injury.

Thirty-three cases of retinal detachment following hockey injury were seen during a 15-year period at the retina clinic of Maisonneuve-Rosemont Hospital, Montreal. Most injuries occurred in adolescents, the average age being 18 years. The mean interval between injury and preoperative examination was 3 years. Almost half of these young hockey players remained legally blind in the affected eye even after a successful operation. A helmet with a protective face visor is suggested as the best prevention against severe ocular damage such as retinal detachment.     

Genomewide scan in Ashkenazi Jewish families demonstrates evidence of linkage of ocular refraction to a QTL on chromosome 1p36

The development of refractive error is mediated by both environmental and genetic factors. We performed regression-based quantitative trait locus (QTL) linkage analysis on Ashkenazi Jewish families to identify regions in the genome responsible for ocular refraction. We measured refractive error on individuals in 49 multi-generational American families of Ashkenazi Jewish descent. The average family size was 11.1 individuals and was composed of 2.7 generations. Recruitment criteria specified that each family contain at least two myopic members. The mean spherical equivalent refractive error in the sample was −3.46D (SD=3.29) and 87% of individuals were myopic. Microsatellite genotyping with 387 markers was performed on 411 individuals. We performed multipoint regression-based linkage analysis for ocular refraction and a log transformation of the trait using the statistical package Merlin-Regress. Empirical genomewide significance levels were estimated through gene-dropping simulations by generating random genotypes at each of the 387 markers in 200 replicates of our pedigrees. Maximum LOD scores of 9.5 for ocular refraction and 8.7 for log-transformed refraction (LTR) were observed at 49.1 cM on chromosome 1p36 between markers D1S552 and D1S1622. The empirical genomewide significance levels were P=0.065 for ocular refraction and P<0.005 for LTR, providing strong evidence for linkage of refraction to this locus. The inter-marker region containing the peak spans 11 Mb and contains approximately 189 genes. Conclusion: We found genomewide significant evidence for linkage of refractive error to a novel QTL on chromosome 1p36 in an Ashkenazi Jewish population.     

Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330)

We present a family with autosomal-dominant inheritance of renal insufficiency caused by renal hypoplasia in six individuals. In all affected individuals, signs of optic disk dysplasia were detected, but most patients were asymptomatic. A heterozygous missense mutation in the PAX2 gene causing a Gly75 to Ser substitution was present in all affected individuals. A second, unrelated patient presented with ocular complaints related to optic disk dysplasia, and had a history of vesico-ureteral reflux. A heterozygous hexanucleotide duplication in the PAX2 gene was detected leading to the duplication of GluThr at positions 74 and 75. The mutations in these two families are the first mutations in the PAX2 gene that do not lead to a truncated protein. Mechanistically, these mutations are expected to result in abnormal folding of the PAX2 protein. These observations further expand the spectrum of clinical features associated with PAX2 mutations, and suggest that a distinct genetic disorder can be identified in patients with renal dysplasia through a careful eye examination. As the ocular manifestations in this syndrome are variable anomalies of retinal and optic disk dysplasia, we prefer the term “papillo-renal syndrome”. Received: 29 January 1998 / Accepted: 25 March 1998     

Ocular Signs Correlate Well with Disease Severity and Genotype in Fabry Disease

Ocular signs in Fabry disease have generally been regarded to be primarily of diagnostic value. We explored whether ocular findings, alone or in particular in combination with the α-galactosidase A gene mutation, have predictive value for disease severity. Data from the Fabry Outcome Survey (FOS), a large, global database sponsored by Shire, were selected for adult patients who had undergone ophthalmological examination. Three ocular signs were assessed: cornea verticillata, tortuous conjunctival and/or retinal vessels, and cataract. Fabry disease severity was measured using FOS Mainz Severity Score Index and modifications thereof. Ophthalmological data were available for 1203 (699 female, 504 male) adult patients with eye findings characteristic of Fabry disease in 55.1%. Cornea verticillata had a similar distribution in women (51.1%) and men (50.8%), whereas tortuous vessels and Fabry cataract were somewhat more frequent in men than in women. Patients with cornea verticillata, selected as the principal ocular sign for this study, had more severe disease (median score, 20.0) versus those without ocular signs (11.0; P<0.001). This finding could be confirmed by applying age adjusted severity scores. Moreover, the prevalence of cornea verticillata was significantly higher in patients with null (male, 76.9%; female, 64.5%) and missense (male, 79.2%; female, 67.4%) mutations versus mild missense (male, 17.1%; female, 23.1%) and the p.N215S (male, 15.0%; female, 15.6%) mutations (P<0.01). Our analyses show a correlation between the prevalence of ocular changes in Fabry disease and disease severity. Consequently, information on ocular findings and α-galactosidase A gene mutation may help assess the risk for more severe Fabry disease. These observed findings are of notable clinical importance, as Fabry disease is characterized by high clinical course variability and only weak genotype-phenotype correlation at the individual patient level. Further confirmatory studies are needed.     

Detection of Ocular Toxoplasma gondii Infection in Chronic Irregular Recurrent Uveitis by PCR

Toxoplasma gondii is a zoonotic parasite resulting in human infections and one of the infectious pathogens leading to uveitis and retinochoroiditis. The present study was performed to assess T. gondii infection in 20 ocular patients with chronic irregular recurrent uveitis (20 aqueous humor and 20 peripheral blood samples) using PCR. All samples were analyzed by nested PCR targeting a specific B1 gene of T. gondii. The PCR-positive rate was 25% (5/20), including 5% (1) in blood samples, 25% (5) in aqueous humor samples, and 5% (1) in both sample types. A molecular screening test for T. gondii infection in ocular patients with common clinical findings of an unclear retinal margin and an inflammatory membrane over the retina, as seen by fundus examination, may be helpful for early diagnosis and treatment.