Hatem Kalantan

Analysis of the SOD1 Gene in Keratoconus Patients from Saudi Arabia

Abstract We investigated Saudi patients with familial and sporadic Keratoconus for mutations in the Superoxide dismutase 1, soluble (SOD1) gene. We sequenced the entire coding region, exon-intron boundaries and intron 2 encompassing a 7-bp deletion in clinically confirmed Keratoconus patients (n = 55) and 100 ethnically matched healthy controls. All cases and controls were unrelated. Sequencing the SOD1 gene revealed the presence of four nucleotide changes and all were non-coding. Those were g.12035 C > A; g.13978 T > A; g.12037 G > A and g.11931 A > C with similar frequencies in patients and controls. All four sequence changes were benign polymorphisms with no apparent clinical significance. Additionally, the 7-bp deletion in intro2 reported previously, were not detected in any of our Keratocnus cohort. In our Keratoconus cohort, no pathogenic SOD1 mutation(s) was identified.

Mitochondrial sequence changes in keratoconus patients.

PURPOSE We investigated whether a group of patients with keratoconus (KTCN) harbor mutations in the mitochondrial genome. METHODS We sequenced the full mitochondrial genome in a group of Saudi patients with KTCN (n = 26) and 100 ethnically matched controls who had no KTCN by examination. RESULTS A total of 10 KTCN patients (38.5%) had potentially pathogenic nonsynonymous mtDNA mutations. Of the nonsynonymous sequence changes detected, 4 (40%) were in Complex I, one was in the tRNA(Glutamine), one was in tRNA(Tryptophan), one was in tRNA(Asparagine), one was in tRNA(Histidine), and two were in the tRNA(Leucine2). One nonsynonymous sequence change was heteroplasmic, whereas all the remaining 9 were homoplasmic. These sequence changes were not detected in controls of similar ethnicity. Four sequence changes were novel (were not reported previously) and 5 were reported previously. Additionally, we detected 54 synonymous (does not result in an amino acid change) sequence changes with no pathologic significance. CONCLUSIONS If our results are confirmed in a larger cohort and multiple ethnicities, then mtDNA mutation may be considered as a genetic risk factor contributing indirectly through the oxidative stress mechanism to the development and/or progression of KTCN.

A prospective, randomised comparison of probing versus bicanalicular silastic intubation for congenital nasolacrimal duct obstruction

Purpose To compare the success rates of probing versus bicanalicular silastic intubation as the primary treatment for congenital nasolacrimal duct obstruction (CNLDO) in children ≥1 year old. Study design Prospective, randomised, comparison. Methods Participants were randomised to undergo probing or bicanalicular silastic intubation. In bilateral cases, the right eye was used for analysis. The procedure was considered successful when all preoperative manifestations disappeared with normal dye disappearance test and a positive Jones primary dye test at least 6 months postoperatively. Secondary outcomes were risk factors for failure. Outcomes were compared between treatments with p<0.05 indicating statistical significance. Results 207 eyes of 181 children between 1 and 8 years old with CNLDO who had not undergone previous surgical treatment were included in the study. 88 eyes underwent probing with a 84.1% success rate and 93 eyes that underwent bicanalicular silastic intubation had a 89.2% success rate (p=0.429). For simple CNLDO, there was a 94.2% (65/69) success rate with probing and a 90.9% (60/66) success rate with bicanalicular silastic intubation (p=0.687). In complex CNLDO, there was a 47.4% (9/19; p=<0.001) success rate with probing and an 85.2% (23/27; p=0.419) success rate with silastic intubation (p=0.016). Age was not a risk factor for failure in either procedure. Conclusions Probing for simple CNLDO in young children is adequate. Bicanalicular silastic intubation seems to have a role in achieving successful outcomes in complex CNLDO.

Traumatic globe rupture after deep anterior lamellar keratoplasty

We report a case of traumatic globe rupture following blunt trauma in the left eye of a 20-year-old male who had undergone deep anterior lamellar keratoplasty for keratonus. Prolapse of both, the crystalline lens and the vitreous was present through the inferior 180 degrees donor host junction. After repositioning, anterior vitrectomy and repair of graft host junction, the graft regained clarity in eight weeks and there was good visual recovery.

Association of mitochondrial haplogroups H and R with keratoconus in Saudi Arabian patients.

PURPOSE Keratoconic corneas exhibit more mitochondrial DNA (mtDNA) damage than do normal corneas and thus mtDNA may represent a potential candidate for genetic susceptibility studies in keratoconus. To test this hypothesis we determined mitochondrial haplogroups in Saudi patients with keratoconus and healthy controls of same ethnicity. METHODS Mitochondrial haplogrouping was performed by polymerase chain reaction-based automated Sanger sequencing in 114 patients with keratoconus and 552 healthy controls. RESULTS Mitochondrial haplogroups H and R were significantly overrepresented in patients with keratoconus (28.9% vs. 8.5%, P < 0.0001 and 17.5% vs. 3.1%, P < 0.0001, respectively) as compared to healthy controls. CONCLUSIONS Our data suggest that individuals with mitochondrial haplogroups H and R are at increased risk to develop keratoconus. In addition, the results provide further evidence for a plausible role of mtDNA in keratoconus etiology.

Posterior polar cataract: A review

Posterior polar cataract is a rare form of congenital cataract. It is usually inherited as an autosomal dominant disease, yet it can be sporadic. Five genes have been attributed to the formation of this disease. It is highly associated with complications during surgery, such as posterior capsule rupture and nucleus drop. The reason for this high complication rate is the strong adherence of the opacity to the weak posterior capsule. Different surgical strategies were described for the handling of this challenging entity, most of which emphasized the need for gentle maneuvering in dealing with these cases. It has a unique clinical appearance that should not be missed in order to anticipate, avoid, and minimize the impact of the complications associated with it.

Pupillary block glaucoma in phakic perfluoropropane gas filled eye

Gas is widely used in vitreoretinal surgery. It is a valuable tool to treat difficult retinal detachments and severe cases of proliferative vitreous retinopathy.1 Gas mediated pupillary block and iridocorneal apposition are known complications in aphakic eyes that underwent vitreoretinal surgery.2–4 We report a case of a phakic patient with an acute pupillary block glaucoma related to the migration of perfluoropropane (C3F8) into the anterior chamber. We are unaware of previous reports on this complication, and a Medline search found no literature on this topic. A 46 year old man underwent a pars plana vitrectomy with 15% C3F8 (perfluoropropane) injection to his right eye for a macula on recurrent rhegmatogenous retinal detachment. There was no history of trauma. During discharge on the first …

Development and Validation of an Arabic Version of the Visual Functioning Index VF-14 for Cataract Patients

Purpose: To develop and validate an Arabic version of the Visual Functioning Index (VF-14) for patients with cataracts. Materials and Methods: The VF-14 was translated into Arabic by an epidemiologist and an ophthalmologist, both fluent in Arabic and English. The VF-14 was administered to patients diagnosed with cataract at two hospitals in Egypt and two hospitals in Saudi Arabia. Patients were also administered three other forms; the cataract symptoms score (CSS); global measure of vision; and cataract medical form. Internal reliability and external validity were measured. Index sensitivity to visual acuity was detected and potential effective factors were investigated. Correlation analyses were performed. A p value less than 0.05 was considered statistically significant. Results: The translated VF-14 was consistent and reliable (σ = 0.763, p < 0.0001). It was also statistically significantly sensitive to vision (p < 0.0001). The mean calculated index was 62.18 ± 19.34, and was highly correlated with; CSS and other scores (p < 0.0001, all cases). Factors that may affect the index are; age, sex, vision, wearing glasses, type, position, and severity of cataract. Conclusion: The Arabic VF 14 is a reliable and valid tool for evaluation of both visual functioning and quality of visual life among cataract patients. It is also sensitive to changes in visual acuity, demographic, and clinical characteristics.

Association of increased levels of plasma tumor necrosis factor alpha with primary open-angle glaucoma

Purpose Retinal ganglion cell (RGC) death is a key feature of glaucoma. Elevated levels of tumor necrosis factor alpha (TNF-α), a pro-inflammatory cytokine, can induce RGC apoptosis and play a critical role in glaucomatous neurodegeneration. Based on the possible role of inflammation and oxidative stress in the pathogenesis of primary open-angle glaucoma (POAG), we investigated the association between plasma levels of TNF-α and POAG or its clinical indices in comparison to non-glaucomatous controls. Patients and methods In a case–control retrospective cohort of 51 POAG cases and 88 controls, plasma TNF-α levels were measured using an enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicates on an automated ELISA analyzer. Results Mean TNF-α level was significantly elevated in POAG cases (1.88 ± 2.17 pg/mL) than the controls (0.93 ± 1.49 pg/mL; p = 0.003). The overall dose–response trend was significant (χ2 = 6.12, df = 2; p = 0.047). No statistical difference was seen in age, gender and systemic disease distribution. A modest negative and significant correlation was seen between TNF-α level and number of antiglaucoma medications, an important clinical index of POAG severity. Moreover, logistic regression analysis showed that the risk of POAG was most significantly affected by TNF-α level and not by age and sex. Conclusion High systemic level of an inflammatory cytokine, TNF-α, is associated with POAG; however, its possible use as a biomarker for early glaucoma diagnosis and/or disease severity needs further investigation.

Elevated levels of plasma tumor necrosis factor alpha in patients with pseudoexfoliation glaucoma

Background Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine, which plays a role in glaucomatous neurodegeneration. Based on the plausible role of inflammation in the pathogenesis of pseudoexfoliation glaucoma (PEG), we investigated whether there is any relationship between the levels of plasma TNF-α and PEG or any of its clinical indices in comparison to normal controls. Methods The study was designed as a retrospective analysis. Plasma samples from 49 PEG patients and 88 non-glaucomatous controls were evaluated for TNF-α levels using an enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicates on a biochemical/ELISA analyzer. Results The two study groups were similar in age, sex and systemic disease distribution. The mean TNF-α concentration was significantly higher in the PEG patients (5.54±4.58 pg/mL) than in the control subjects (0.93±1.49 pg/mL; 95% confidence interval [CI] =3.50–5.72; p=0.000). The overall dose–response trend was significant (χ2=57.07, df=2; p=0.000). A moderate positive and significant correlation was seen between TNF-α level and cup/disc ratio, an important clinical index for PEG. Besides, binary logistic regression analysis showed that the risk of PEG was most significantly affected by TNF-α level as compared to no association with age and sex. In receiver operating characteristic analysis, the area under the curve was 0.777 (95% CI =0.682–0.872) and statistically significant (p=0.000). Conclusion Elevated systemic levels of inflammatory marker, TNF-α, are associated with PEG and may possibly serve as a biomarker for undiagnosed early glaucoma and/or as a marker for disease progression.