Meesmann corneal epithelial dystrophy in a Saudi Arabian family.

PURPOSE: Meesmann corneal epithelial dystrophy is a dominantly inherited disorder that was originally reported in Germany and later in descendants of German immigrants to the United States. We report Meesmann corneal epithelial dystrophy in a family that cannot be traced to Germanic origin. METHODS: A 17-year-old Saudi boy from the Al-Qahtani tribe of the Asir region of the kingdom came to the King Khaled Eye Specialist Hospital with classic clinical findings of Meesmann corneal epithelial dystrophy. We examined all members of the immediate family of the index case and members of five branches of the extended family. RESULTS: Meesmann corneal epithelial dystrophy was present in the father and one sister of the index case. Four additional affected individuals were identified in three generations of one branch of the extended family. All but one of the seven affected individuals were aged 17 years or older. Our findings are consistent with previous reports of an autosomal dominant pattern of inheritance, with probable incomplete penetrance or delayed onset of phenotypic expression. CONCLUSION: We report Meesmann corneal epithelial dystrophy in a family without German ancestry.

Orbital volume augmentation with subperiosteal room-temperature-vulcanized silicone implants: a clinical and histopathologic study.

Enophthalmos, a clinical feature of the anophthalmic orbit, often produces a considerable cosmetic deformity. Management of this condition includes surgical volume augmentation with orbital implants. Several types of materials with different shapes have been used with variable success rates. Between 1984 and 1990, we treated 84 anophthalmic patients with room temperature vulcanized (RTV) subperiosteal silicone implants. Adequate volume augmentation and correction of the apparent enophthalmos was achieved in 75 patients. Extended patient follow-up, analysis of data and results, histopathologic assessment of implant capsules, and management of complications have provided a unique opportunity to study the efficacy of the surgery. We present our experience in the management of this condition.

Extracapsular cataract extraction with or without posterior chamber intraocular lenses in eyes with cataract and high myopia.

PURPOSE: To compare the results of insertion of low-power or zero-power posterior chamber intraocular lenses (PC IOLs) after cataract extraction in eyes with high myopia with leaving the eye aphakic. METHODS: The outcome of extracapsular cataract extraction (ECCE) with low-power or zero-power PC IOLs in 184 consecutive highly myopic (axial length = 26.0 mm or longer) eyes was compared with 184 consecutive highly myopic eyes receiving ECCE without PC IOLs. Axial length, preoperative visual acuity, age, sex, and follow-up were similar between both groups. RESULTS: In the pseudophakic eyes, there was a statistically significantly better visual outcome (P = 0.006), decreased incidence of posterior capsule opacification (13.6% versus 33.2%, P < 0.01), and decreased requirement for YAG capsulotomy (6.5% versus 17.9%, P < 0.01). There were two retinal detachments in the pseudophakic eyes compared with four in the aphakic eyes. There were no sight-threatening complications in 12 pseudophakic eyes after YAG capsulotomy. There were four sight-threatening complications (2 retinal detachments, 2 cases of uveitis with secondary glaucoma) in 33 aphakic eyes after YAG capsulotomy. CONCLUSIONS: The use of PC IOLs may result in a lower complication rate and better visual outcome after ECCE in eyes with cataract and high myopia.

Prevalence and causes of visual impairment and blindness in the south western region of Saudi Arabia.

A population-based survey of the prevalence of major causes of blindness and visual impairment was conducted in Bisha region, Saudi Arabia. Overall, 2882 people were examined. The prevalence of blindness (visual acuity of < 3/60 in the better eye with best available correction) was 0.7% and the prevalence of visual impairment (visual acuity < 6/12 but > or = 3/60 in the better eye with best available correction) was 10.9%. Cataracts were responsible for 52.6% of blindness and 20.6% of visual impairment. Refractive errors accounted for 67.9% of visual impairment. Proper management of cataracts and correction of refractive errors will cure 73.6% of blind subjects and 88.5% of visually handicap people in this part of the world.

Phacoemulsification at King Khaled Eye Specialist Hospital--the experience of the past.

OBJECTIVE: To study the outcome of phacoemulsification (PE) compared to standard extracapsular surgery before the introduction of state-of-the-art techniques (capsulorhexis, hydrodissection, nuclear cracking, nuclear chopping, sutureless incisions) and sophisticated equipment. STUDY DESIGN: Charts from 375 patients (453 eyes) undergoing PE between 1984 and 1989 were randomly selected and studied retrospectively. A minimum age of 35 years, and a minimum follow-up of three months were required. SETTING: A large eye hospital in the Kingdom of Saudi Arabia staffed with an international faculty of ophthalmic surgeons. PATIENTS: Patients over 35 years of age undergoing PE for immature, mature and traumatic cataract. MAIN OUTCOME MEASURES: Postoperative visual acuity, and rate or frequency of intraoperative complications. RESULTS: 66.5% achieved visual acuity of 20/40 or better, which compares favourably with the 36.5% of eyes reaching this level of visual acuity after mainly standard extracapsular cataract surgery in another study at our hospital. Posterior capsule ruptures occurred in 7.5% and vitreous loss in 5.5%. Other ocular disease (odds ratio 7.51 confidence interval 4.43-12.7) and intraoperative complications (odds ratio 2.97 confidence interval 1.38-6.42) were statistically significant predictors for final visual acuity of under 20/40 (p = < 0.001 and 0.005 respectively). CONCLUSION: The outcome of PE was better than that of standard extracapsular cataract extraction in the same setting. However, since PE appeared to be used selectively, no clear advantage compared to extracapsular cataract extraction is evident in the period before the introduction of modern state-of-the-art PE-techniques.

Simultaneous high-performance liquid chromatography analysis of azithromycin and two of its metabolites in human tears and plasma.

This article describes a high-performance liquid chromatographic (HPLC) method for the measurement of azithromycin (AZI) and two of its metabolites, 9a-N-desmethylazithromycin (ADES) and N-desmethylazithromycin (NDES), in human tears and plasma. The drug, metabolites, and internal standard (n-propylazithromycin [IS]) were detected electrochemically after injection of the extracted sample into the HPLC system. The peak height ratio (AZI, ADES, or NDES to IS) varied linearly, with concentrations in the ranges of 0.1 mg/L to 2.0 mg/L (tears) and 0.01 mg/L to 2.0 mg/L (plasma) of AZI, ADES, and NDES; the correlation coefficient (r) was more than 0.994 mg/L for all of the compounds (n=6). The analysis of tear samples collected at different intervals within 12 hours to 144 hours after a dose of 20 mg/kg of AZI from a trachoma patient yielded concentrations ranging from 1.52 mg/L to 0.34 mg/L for AZI, 0.79 mg/L to 0.27 mg/L for ADES, and 1.99 mg/L to less than 0.20 mg/L for NDES. The concentration of AZI in plasma ranged from 0.15 mg/L to 0.01 mg/L, whereas ADES and NDES were undetectable.

Pharmacokinetics of azithromycin in trachoma patients: serum and tear levels.

OBJECTIVE: To determine the effectiveness of single-dose oral azithromycin in the treatment of Chlamydia trachomatis through monitoring of tear and serum levels. DESIGN: Nonrandomized, clinical trial. PARTICIPANTS: Fourteen school-age children with active trachoma (one failed to complete the study). INTERVENTION: A single dose of azithromycin (20 mg/kg) was administered orally to 14 patients, and tear and serum levels were determined with high-performance liquid chromatography at 12, 24, 48, 72, 96, 120, and 144 hours after administration. MAIN OUTCOME MEASURES: Azithromycin levels in tears and serum. RESULTS: Peak levels of 1.53 microg/ml (standard deviation [SD] +/- 0.94) and 0.15 microg/ml (SD +/- 0.04) were obtained at 12 hours in both tears and serum, gradually decreasing over 144 hours. All patients were disease-free by 6 months. CONCLUSIONS: Levels of azithromycin in patients with trachoma were found to be within minimum inhibitory concentration range for Chlamydia trachomatis (0.03-0.25 microg/ml) throughout the monitored period of 6 days.

Workup for metastatic retinoblastoma. A review of 261 patients.

PURPOSE: The means available to screen for retinoblastoma metastases, including bone marrow aspiration, lumbar puncture, and radionuclide scans, offer variable usefulness at different stages of the disease. In this study, the authors attempted to assess the value of these tests as part of the initial workup for metastases. METHODS: Medical files of 261 patients with retinoblastoma were reviewed, and the results of bone marrow, lumbar puncture, and bone and liver radionuclide scans were correlated with the laterality, clinical staging, and histopathologic findings. The presence or absence of tumor in the choroid and the optic nerve also were correlated with the results of diagnostic tests. RESULTS: Of 261 patients with retinoblastoma, 147 (56.3%) and 114 (43.7%) had unilateral and bilateral disease, respectively; 11.6% of unilateral cases and 14.9% of bilateral cases had distant metastasis (P = 0.2). Bone marrow aspirations were performed on 101 patients (38.7%), and 10 (9.9%), of these specimens showed the presence of retinoblastoma cells in the aspirate. Ninety-four (36%) of the patients were examined with spinal tap cytology, and the results of four (4.3%) of these were positive for tumor cells. Radionuclide bone and liver scans were performed on 49 (18.8%) and 48 (18.4%) patients, respectively; 5 (10.2%) had abnormal bone scans and 3 (6.2%) had abnormal liver scans. The average age in the metastatic group was 3.1 years, whereas the average age in the nonmetastatic group was 2.3 years. All of our abnormal test results were found in patients with stages III and IV disease, with the exception of one abnormal lumbar puncture in a patient with stage II disease. The correlation of diagnostic tests with the histopathologic findings showed that with no choroidal involvement, no positive diagnostic tests were encountered. Correlation between positive diagnostic test results and the level of optic nerve involvement failed to indicate any trends. CONCLUSION: Our study indicated a good interrelation between the positivity of diagnostic tests (bone marrow and bone scan) and higher stages of the disease (stages III and IV) and choroidal involvement in enucleated eyes, with statistically significant correlations; correlations with lumbar puncture and liver scan were not significant.

Multiple CYP1B1 mutations and incomplete penetrance in an inbred population segregating primary congenital glaucoma suggest frequent de novo events and a dominant modifier locus.

Primary congenital glaucoma (PCG) is an autosomal recessive disorder associated with unknown developmental defect(s) in the anterior chamber. Recently, we reported three distinct mutations in CYP1B1, the gene for cytochrome P4501B1, in 25 Saudi families segregating PCG. For this report, we analyzed 37 additional families and confirmed the initial finding of decreased penetrance. Mutations and intragenic single-nucleotide polymorphisms (SNPs) were also analyzed from direct sequencing of all CYP1B1 coding exons. Eight distinct mutations were identified: G61E, R469W and D374N, the most common Saudi mutations, account for 72, 12 and 7%, respectively, of all the PCG chromosomes. Five additional homozygous mutations (two deletions and three missense mutations) were detected, each in a single family. Affected individuals from five families had no CYP1B1 coding mutations, and each family had a unique SNP profile. The identification of eight distinct mutations in a single gene, on four distinct haplotypes, suggests a relatively recent occurrence of multiple mutations in CYP1B1 in Saudi Arabia. These data demonstrate decreased penetrance of the PCG phenotype in the Saudi population, because 40 apparently unaffected individuals in 22 families have mutations and haplotypes identical to their affected siblings. Two individuals were subsequently diagnosed with glaucoma and two others had abnormal ocular findings that are consistent with milder forms of glaucoma. Analysis of these 22 kindreds suggests the presence of a dominant modifier locus that is not linked genetically to CYP1B1. Linkage and Southern analyses excluded three candidate modifier loci.

A novel locus for Leber congenital amaurosis on chromosome 14q24.

Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous autosomal recessive retinal dystrophy and the most common genetic cause of congenital visual impairment. We used a DNA pooling strategy comparing the genotypes of affected to unaffected control pools in a genome-wide search for identity-by-descent on a consanguineous Saudi Arabian LCA family. A shift to homozygosity was observed in the affected DNA pool compared with the control pool at linked markers D14S606 and D14S610. Genotyping of individual DNA samples from the entire pedigree for marker D14S74, closely linked to these loci, and several flanking markers confirmed linkage with a ZMAX=13.29 at theta=0.0. These data assign a third locus (LCA3) for LCA to chromosome 14q24. This locus and the previously identified loci are excluded for other Saudi Arabian pedigrees, both confirming that this clinical disorder is genetically heterogeneous and that additional LCA genes remain to be identified.

Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13.

The extraocular fibrosis syndromes are congenital ocular-motility disorders that arise from dysfunction of the oculomotor, trochlear, and abducens nerves and/or the muscles that they innervate. Each is marked by a specific form of restrictive paralytic ophthalmoplegia with or without ptosis. Individuals with the classic form of congenital fibrosis of the extraocular muscles (CFEOM1) are born with bilateral ptosis and a restrictive infraductive external ophthalmoplegia. We previously demonstrated that CFEOM1 is caused by an autosomal dominant locus on chromosome 12 and results from a developmental absence of the superior division of the oculomotor nerve. We now have mapped a variant of CFEOM, exotropic strabismus fixus ("CFEOM2"). Affected individuals are born with bilateral ptosis and restrictive ophthalmoplegia with the globes "frozen" in extreme abduction. This autosomal recessive disorder is present in members of three consanguineous Saudi Arabian families. Genetic analysis of 70 individuals (20 affected individuals) reveals linkage to markers on chromosome 11q13, with a combined LOD score of 12.3 at the single nonrecombinant marker, D11S1314. The 2.5-cM CFEOM2 critical region is flanked by D11S4196/D11S4162 and D11S4184/1369. Two of the three families share a common disease-associated haplotype, suggesting a founder effect for CFEOM2. We hypothesize that CFEOM2 results from an analogous developmental defect to CFEOM1, one that affects both the superior and inferior divisions of the oculomotor nerve and their corresponding alpha motoneurons and extraocular muscles.

Fundus albipunctatus and retinitis punctata albescens in a pedigree with an R150Q mutation in RLBP1.

Fundus albipunctatus (FA; OMIM 136880) is a rare form of apparently stationary night blindness characterized by the presence of myriad symmetrical round white dots in the fundus with a greater concentration in the midperiphery. A distantly similar but distinct clinical entity, retinitis punctata albescens (RPA), is also characterized by aggregation of irregular white flecks but is progressive and evolves to generalized atrophy of the retina. We studied 4 consanguineous kindreds diagnosed with FA from Saudi Arabia. Given the substantial phenotypic variation and overlap between different flecked retinal dystrophies, we evaluated all known genes associated with such conditions by both genetic analysis and direct sequencing. In one kindred, KKESH-099, we identified a homozygous R150Q alteration in RLBP1, the gene encoding the cellular retinaldehyde binding protein, associated previously with both recessive retinitis pigmentosa (arRP) and RPA. Examination of several patients aged 3-20 years over a 9-year period presented no evidence for either RP or RPA. In contrast, clinical examination of individuals with the same mutation in their fourth and fifth decade revealed signs consistent with RPA. The data suggest that the R150Q mutation in RLBP1 may result in RPA with slow progression. More importantly, younger individuals diagnosed with the milder disorder FA thought to be stationary may evolve to a more devastating and progressive phenotype.

Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia.

The autosomal recessive disorder primary congenital glaucoma (PCG) is caused by unknown developmental defect(s) of the trabecular meshwork and anterior chamber angle of the eye. Homozygosity mapping with a DNA pooling strategy in three large consanguineous Saudi PCG families identified the GLC3A locus on chromosome 2p21 in a region tightly linked to PCG in another population. Formal linkage analysis in 25 Saudi PCG families confirmed both significant linkage to polymorphic markers in this region and incomplete penetrance, but it showed no evidence of genetic heterogeneity. For these 25 families, the maximum combined two-point LOD score was 15.76 at a recombination fraction of .021, with the polymorphic marker D2S177. Both haplotype analysis and homozygosity mapping in these families localized GLC3A to a 5-cM critical interval delineated by markers D2S2186 and D2S1356. Sequence analysis of the coding exons for cytochrome P4501B1 (CYP1B1) in these 25 families revealed three distinctive mutations that segregate with the phenotype in 24 families. Additional clinical and molecular data on some mildly affected relatives showed variable expressivity of PCG in this population. These results should stimulate a study of the genetic and environmental events that modify the effects of CYP1B1 mutations in ocular development. Furthermore, the small number of PCG mutations identified in this Saudi population makes both neonatal and population screening attractive public health measures.