Tear function abnormalities in down syndrome

Down syndrome is a common chromosomal anomaly, characterized by specific facial features, eye anomalies with repeated ophthalmic infections. The integrity of the ocular surface is maintained by the tear film. To determine the presence of tear function changes in children with Down syndrome and their relation with the development of ophthalmic diseases. Tear film was evaluated by the ferning test and breakup time [BUT] measurement in 23 patients [46 eyes] confirmed as having Down syndrome by cylogenetic analysis and 20 normal control children [40 eyes] with matched age and sex. There was an alteration in both ferning and BUT tests in children with Down syndrome compared to controls. Abnormal ferning test was found in 28 out of 46 tear samples from the patient's eyes compared to 2 out of 40 normal control eyes. BUT test results showed that the preocular tear film stability was poor in 65.2% of patients' eyes, average in 26.1% and good in only 8.7% of their eyes; while controls had good and average tear film stability each representing 50% of eye's number. These tear function abnormalities may have a role in the frequent infectious pathologies found in the anterior eye segment in patients with Down syndrome which necessitates applying new stringent strategies for ophthalmologic care and management of these patients

Ophthalmogenetic and epidemiological studies of Egyptian children with mental retardation

Mental retardation [MR] is a congenital or early onset lifelong impairment of cognitive adaptive functioning or daily living skills. It is a serious and lifelong disability that places heavy demands on society and the health system. The prevalence of visual and ocular disorders in children with MR is high and can influence sensory-motor development and learning ability. Assessment of the genetic and epidemiologic aspects of mental retardation and clarifying the ocular and visual problems among mentally disabled children. A cross-sectional hospital based study was conducted, through a period of two years, included 190 children under 18 years of age with mild to profound intellectual disabilities who were diagnosed among 480 cases referred to the Genetic clinic, Research Institute of Ophthalmology for genetic diagnosis and counseling. The definition of MR and the criteria for diagnosis were adopted from the World Health Organization [WHO] classification. The etiology of MR was specified by obtaining information about the personal and family history that included a three generation pedigree analysis, with special attention to the presence of similar cases, thorough clinical examination including complete neurological evaluation, chromosomal and other investigative studies. Ophthalmologic examination included visual acuity testing, ocular motility and examination of the external eye and anterior segment; cycloplegic refraction and fundus examination. One hundred and ninety patients representing 39.6% of the total examined cases in two years were classified etiologically into 6 groups. Specific causes were found in 161 cases [84.7%] and the etiology was unknown in 15.3% of children. Metabolic and chromosomal disorders comprised the most common etiological problems of the examined mentally retarded children in this study. The percentage of mild, moderate, severe and profound MR was 67.5%, 26%, 5.8% and 0.7%, respectively. Family history was positive in 34.7% of patients and autosomal recessive inheritance was the commonest mode of transmission [48.4%] that reflects the high percentage of consanguineous marriages among Egyptians. Microscopically visible chromosomal anomalies of intellectually disabled patients included 25 numerical and 11 structural aberrations. Errors of refraction and strabismus were the most common in children with chromosomal disorders [24.7%] and [28.1%] respectively. While the highest percentage of optic atrophy, retinal dystrophy, microphthalmia, cataract and corneal opacities were diagnosed in children with metabolic disorders representing 76.2%, 93.3%-, 38.5%, 50% and 80% of cases diagnosed in all categories respectively. In this study, metabolic and chromosomal disorders represented the most common etiological problems among the examined mentally retarded children with the highest proportion of specific ocular and visual problems represented among them to the extent that the eye could be considered as a window for their diagnosis. In most cases, diagnosis will assist families in understanding the condition, its prognosis and recurrence risks; more epidemiological studies have to be undertaken to determine the magnitude of the problem and its pattern of distribution in our country. The results also emphasize the need for establishing an efficient system to provide regular ophthalmic care for children with mental retardation

Selected predictors of apoptosis in retinitis pigmentosa

The genetics of non syndromic retinitis pigmentosa [RP] is complex with numerous gene mutations. An attempt to overcome each individual mutation provides an overwhelming challenge. However targeting apoptosis which represents a final common pathway to photoreceptor cell death may provide a more practical approach. This study focused on some predictors of apoptosis in RP and their potential usefulness for patients' management and relatives' early diagnosis. Forty nine RP patients with thirty controls were evaluated genetically and ophthalmologicaly with assessment of plasma total nitrite and nitrate [as an index for nitric oxide], Plasma sFas as an index of apoptosis and plasma fatty acids levels. Autosomal recessive RP was the most common type of inheritance and the levels of plasma sFas and nitric oxide [NO] were significantly higher in retinitis pigmentosa compared to controls. Retinitis pigmentosa patients had significantly lower percentage of plasma omega3 fatty acids especially docosahexaenoic acid [DHA] relative to controls. sFas, NO, and DHA could differentiate between RP patients and control subjects with 100%, 100%, 97% sensitivity and 90%, 90%, 100% specificity respectively. sFas and nitric oxide levels were higher in cases of autosomal recessive [AR] type followed by X-linked, autosomal dominant, then simplex cases relative to the control group this may explain why AR and X-Linked forms are clinically more severe. In conclusion; diagnosis and treatment of RP could be aided by systemic markers or predictors of retinal degeneration. The consistent decrease in the plasma omega 3 fatty acids especially DHA, and increase sFas and nitric oxide levels may draw the attention upon the use of these markers as laboratory tests for relatives of affected patients who are at high risk for having retinitis pigmentosa. Also, omega 3 fatty acids in the form of DHA were recommended as possible supplements for the patients and their relatives

Implication of glutathione S-transferase M1 and T1 polymorphisms in the development of senile cataract among Egyptians

Cataract, or opacification of the lens, is one of the most common causes of loss of useful vision among Egyptians. Currently, surgery is the only approach for the treatment of cataract and the etiology of age-related changes in the lens is not fully understood. Oxidative damage and genetic factors have a major role in the development of age related cataract. Glutathione is the most abundant non-protein intracellular thiol, with multiple roles as antioxidant agent, and the glutathione S-transferases [GSTs] are group of polymorphic enzymes that are important in protection against oxidative damage, as they dethiolate protein-S-S-glutathione in the human lens. The study aimed to determine the effect of genetic polyorphisms of Glutathione S-transferases M1 and T1 on the risk of senile cataract in Egyptian population. Using a multiplex polymerase chain reaction [PCR], the GSTM1 and GSTT1 gene polymorphisms were evaluated in 53 Egyptian patients with senile cataract and in 73 otherwise healthy control group with matched age and sex distribution. Serum GST activity, the level of Malondiableyde [a lipid peroxidation product] and the blood level of reduced glutathione [GSH] were estimated. The frequency of the GSTM1 positive individuals among the senile cataract group was significantly higher than in controls [57 vs 37%] with odds ratio 2.22 95% CI:1.08-4.573; p=0.029]. The risk among the GSTM1 positive individuals of developing senile caaract was even higher in female subjects: 68% of females were GSTM1 positive in the cataract group while only 38% of females had GSTM1 positive genotype in controls [OR=3.4; 95% CI: 1.284-9.067; p=0.012]. combination of "GSTM1 positive and GSTT1 positive" genotypes [OR = 2.16; 95% CI: 0998-4.68; P=0.049]. However the combination of "GSTM1 null, GSTT1 positive" was found to be protective from the development of senile cataract [OR=0.47; 95% CI: 0.22-0.99; p=0.045]. The study also showed significantly deceased serum level of GST and reduced glutathione [GSH] and increased level of malondialdehyde [MDA] in senile cataract patients relative to controls [p>0.001]. The present study suggests that the GSTM1 positive genotype and the combined "GSTM1 positive/GSTT1 positive" genotype may be associated with increased risk of development of senile cataract. However the "GSTM1 null/GSTT1 positive" genotype was found to be protective from the development of cataract in the Egyptian population. The correlation between polymorphic GSTs with the other cataractogenic genetic and environmental factors is highly complicated so, the study also, suggests that when evaluating the role of a particular GST gene in any disease susceptibility, the whole pattern of different biotransformation enzymes should be taken into account as much as possible. The importance to further evaluate this matter is related to the possibility of developing diagnostic tool for predicting, by non-invasive genotype analysis, the inter-individual susceptibility to the disease

P53 expression and histopathological changes in primary and recurrent pterygia among Egyptian cases

The aim of this work is to assess P53 expression and histopathologic features in the epithelia of both primary and recurrent pterygia cases, searching for the pathogenesis of this common lesion. The pterygia specimens from 22 patients [twelve primary and ten recurrent cases] were studied by both routine hematoxylin and eosin stain and immunohistochemically using antibodies against P53 protein. Cases included in this study were 16 males and 6 females. Their ages ranged from 20 to 55 years. Positive family history was recorded in 18.2% of patients and positive parental consanguinity in 9.1% of them. Twenty cases [90.1%] had a history of chronic exposure to solar light i.e prolonged outdoor exposure time [8-12 hours/day] for more than 5 years. Epithelial hyperplasia was more common in recurrent pterygium samples [8 cases] than primary pterygium [only one case]. But, squamous metaplasia with mild dysplasia was more common in Primary pterygium samples [10 cases] than recurrent samples [2 cases]. Ten out of twelve studied specimens with primary pterygium [83.4%] were positive for abnormal P53 expression and two specimens [16.6%] were negative, while only 2 specimens [20%] of recurrent pterygium showed the abnormal positive expression and 8 cases [80%] were negative. Cases with marked and moderate P53 immunostaining [12 cases] showed squamous metaplasia with mild dysplastic changes, nine out of ten cases with negative immunostaining showed epithelial hyperplasia and the remaining sample showed squamous metaplasia without dysplasia. P53 protein is expressed at a high rate in primary pterygia as compared to cases of recurrence. Hence the possible role of P53 in the original development of pterygium, suggesting that pterygium could be a result of uncontrolled cell proliferation and unregulated cell apoptosis which can be proposed a type of benign tumour or even a precancerous condition and not as a degenerative lesion. It seems to be no correlation between P53 expression and recurrence. Recurrent pterygium was related to hyperplastic changes and this may explain the pathogenesis of recurrence especially if the pterygium was not excised completely and the remained epithelial cells continued to grow and formed a new pterygium

study of p53 protein and DNA ploidy in retinoblastoma

Retinoblastoma is the most common primary intraocular cancer in children. It arises from cells that are defective in both copies of the retinoblastoma susceptibility gene [RB I]. Loss of both RB1 and p53 functions may be required for cell immortalization and tumor development. The pattern of p53 expression in retinoblastoma appears to depend on the state of differentiation of the tumor. p53 and RB pocket proteins are important to control DNA ploidy, which may have a value in estimating the prognosis of retinoblastoma. The aim of this work was to assess p53 expression, DNA ploidy, and their relations with histopathologic features in retinoblastoma cases. The study was done on eight patients with retinoblastoma [seven males and one female]. Personal and family history with pedigree analysis were done for all cases. Ophthalmic examination with follow up of tumor regression rate during therapy was performed. Eight primary retinoblastoma samples were obtained from enucleated eyes of all patients. Retinoblastoma sections were stained by hematoxylin and eosin stain and scoring of histopathologic features was performed. Sections were immunohistochemically stained for the protein product of the tumor suppressor gene p53 and quantified for the extent and intensity of the staining. DNA ploidy was examined by assessment of type of DNA histogram and DNA index using cytometric analysis system [CAS 200] after feulgen staining. The proliferative activity was automatically expressed by the CAS 200 as the percentage of cells engaged in the S-phase of the cycle. Our results indicated that p53 protein was immunohistochemically detectable in most retinoblastoma cases [7/8 cases], and was only negative in one case. DNA was aneuploid in 6 out of 8 cases, while 2 cases [one of them was p53 negative, and the other showed weak positivity] were diploid with high proliferative activity. Histopathologic examination revealed that 3 cases were poorly differentiated and 5 cases showed intermediate differentiation with increased necrotic changes and mitotic figures. Retinoblastoma samples showed high degree of p53 protein expression and high degree of aneuploidy which were related to the aggressiveness of histopathologic changes of retinoblastoma. Thus both p53 expression and DNA ploidy have been shown to be markers of aggressiveness of tumor behaviour in retinoblastoma and can help in the prediction of its prognosis

Taurine level and field changes in different hereditary types of retinitis pigmentosa

This study was performed to detect if there is a correlation between various hereditary subtypes, taurine level and field indices. This correlation may help in the accurate diagnosis and management of different hereditary subtypes of retinitis pigmentosa cases. The study included 28 patients with retinitis pigmentosa [16 males and 12 females] and 25 controls with matched age and sex distribution. All patients and controls were subjected to clinical evaluation that included personal and family history taking, informative pedigree construction and full clinical examination to exclude the associated genetic syndromes. Field changes were detected in both eyes of 22 RP patients using Humphrey field analyzer 640 utilizing the 24-2 program. All patients and ten of the controls were examined for plasma taurine level by amino acid analyzer [Lc 3000 Eppendorf Biotronik]. A statistical analysis was done using statistical package for social science [SPSS] program. The results showed that taurine level can help in the diagnosis of different hereditary subtypes of retinitis pigmentosa, especially simplex cases that has no definite inheritance. This will improve the genetic counseling for RP families. Taurine can also be considered as a marker for the degree of severity of visual field affection in retinitis pigmentosa cases

Genetic and environmental factors in different types of age-related cataract among Egyptians

The present study included 280 patients with age-related cataract [153 males and 127 females] and 296 controls with similar age and sex distribution. All cases and controls were subjected to thorough personal and family history taking including consanguinity, occupation, residency, diabetes mellitus, hypertension, smoking, family history of age-related cataract and family pedigree analysis. Full clinical examination also included complete ophthalmological evaluation to determine the type of cataract using slit-lamp examination and visual acuity measurement. Seventy-five patients and 25 controls were subjected to the following investigations: Estimation of serum total protein, serum albumin and globulin levels, albumin/globulin [A/G] ratio, hemoglobin [Hb] level and red blood cells [RBCs] count. Statistical analysis was conducted using SPSS program for calculating t test, X2 test and multiple logistic regression analysis. The present study revealed that mixed cataract [i.e. presence of more than one type of cataract] was the commonest type of age-related cataract in Egypt [48.9% of cases]. Positive family history, consanguinity and exposure to ultraviolet irradiation were universal risk factors for all types of cataract among Egyptians. Diabetes mellitus was associated with nuclear and posterior subcapsular types of cataract, while hypertension had its effect on both cortical and posterior subcapsular types. Biochemical analysis revealed that the risk of age-related cataract increases with decreased level of serum total protein, decreased serum albumin and globulin levels, decreased RBCs count and hemoglobin level