Association between Polymorphism rs61876744 in PNPLA2 Gene and Keratoconus in a Saudi Cohort.

The genetic etiology of Keratoconus (KC) in Middle Eastern Arabs of Saudi origin is still unclear. A recent genome-wide study identified two significant loci in the region of PNPLA2 (rs61876744) and CSNK1E (rs138380) for KC that may be associated with KC in the Saudi population. In addition, polymorphisms in the apolipoprotein E (APOE) gene, namely, rs429358 and rs7412, responsible for APOE allelic variants ε2, ε3, and ε4, may influence KC via oxidative stress mechanism(s). Thus, we investigated the possible association of polymorphisms rs61876744, rs138380, rs429358, rs7412, and APOE genotypes in KC patients of the Saudi population. This study included 98 KC cases and 167 controls. Polymorphisms rs6187644 and rs138380 were genotyped using TaqMan assays, and rs429358 and rs7412 were genotyped via Sanger sequencing. Although the allele frequency of rs61876744(T) in PNPLA2 was a protective effect against KC (odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.44-0.93), the p-value (p = 0.020) was not significant for multiple testing correction (p = 0.05/4 = 0.015). However, rs6187644 genotype showed a modestly significant protective effect in the dominant model (OR = 0.53, 95% CI = 0.32-0.88, p = 0.013). Polymorphisms rs138380, rs429358, and rs7412 showed no significant allelic or genotype association with KC. However, the ε2-carriers (ε2/ε2 and ε2/ε3 genotypes) exhibited a greater than 5-fold increased risk of KC, albeit non-significantly (p = 0.055). Regression analysis showed no significant effect of age, gender, and the four polymorphisms on KC. Our results suggest that polymorphism rs6187644 in PNPLA2 might be associated with KC in the Middle Eastern Arabs of Saudi origin but warrant a large-scale association analysis at this locus.

Unilateral keratoconus associated with iridocorneal endothelial syndrome: Case report.

We report a rare association of unilateral keratoconus (KC) and iridocorneal endothelial syndrome in a 34-year-old female. Slit-lamp examination showed advanced KC with faint apical scarring in her right eye. The pupil was superiorly displaced with superior peripheral anterior synechia. Specular microscopy showed abnormal endothelium with low endothelial cell count in the right eye. Corneal topography confirmed the unilateral KC diagnosis. As the patient did not tolerate hard contact lens, penetrating keratoplasty with pupilloplasty was performed with excellent outcome.

Possible Spontaneous Extrusion of a Traumatic Deeply Embedded Intracorneal Foreign Body: A Case Report.

Traumatic intracorneal foreign bodies are very common and account for 30.8% of all ocular injuries. Deeply embedded intracorneal foreign bodies have been documented in association with good final visual outcome when managed effectively. We report herein, an unusual case of possible spontaneously extruded deeply embedded intracorneal foreign body 5 weeks after sustaining a trauma to his right eye. Whether the foreign body was truly spontaneously extruded or absorbed by corneal tissue is unknown.

Teleophthalmology in Saudi Arabia.

Teleophthalmology is the provision of ophthalmic care using digital medical equipment and telecommunications technology. While teleophthalmology has been practiced since the 1990s, it became a crucial medical service during the COVID-19 pandemic when doctors were required to make diagnoses from a distance. This was certainly the case in Saudi Arabia, a relatively large country with limited medical workforce to meet demands, yet a high prevalence of diseases such as diabetes, glaucoma, and cataracts which are considered leading causes of visual impairment. In response to the pandemic, Saudi Arabia's Ministry of Health issued scientific instruction manuals and guidelines for health-care providers which paved the way for increased use of digital technologies and solutions to mitigate the health and economic impacts of COVID-19. The pandemic served to accelerate the use of virtual ophthalmology in Saudi Arabia with the most common teleophthalmology applications being teleconsultation and disease-specific applications such as diabetic retinopathy and retinopathy of prematurity. Although some challenges relating to implementing teleophthalmology in Saudi Arabia remain, it is felt that there are great opportunities to expand the use of telemedicine in ophthalmology in this country.

Bacterial Keratitis: Clinical Features, Causative Organisms, and Outcome During a 13-year Study Period.

PURPOSE: This study aimed to review clinical features, causative organisms, complications, and outcome of bacterial keratitis cases at a tertiary eye hospital. METHODS: A retrospective study was conducted on clinically diagnosed bacterial keratitis cases from 2007 to 2019. Poor outcome was flagged if any of the following was identified: final visual acuity (VA) worse than 20/200, decrease in VA (1 line or worse compared with presenting VA), corneal perforation, endophthalmitis, failed graft, or cases requiring enucleation or evisceration. RESULTS: The study included 263 cases of bacterial keratitis with 169 cases (64.3%) of culture-positive bacterial keratitis. Gram-positive bacteria were found to be the causative organism in 106 cases (62.8%). The most common types were coagulase-negative staphylococci (23.1%) and Pseudomonas (23.1%). Culture-positive bacterial keratitis was associated with the development of anterior chamber reaction (≥1+) on multivariate analysis [adjusted odds ratio (OR): 3.03, confidence interval (CI): 1.23-7.45, P = 0.016]. The complications that occurred in the current cohort included visually significant scar (64.7%), perforation (10.8%), cataract (8.8%), nonhealing epithelial defects (8.0%), corneal neovascularization (4.9%), endophthalmitis (4.6%), and hypotony (1.5%). On multivariate analysis, diabetes mellitus (adjusted OR: 3.51, CI: 1.59-7.76, P = 0.002), poor presenting best-corrected VA (adjusted OR: 3.95, CI 1.96-7.96, P < 0.001), and positive cultures (adjusted OR: 2.36, CI: 1.11-5.00, P = 0.025) were associated with poor outcome. CONCLUSIONS: Culture-negative keratitis had less severe infection and better outcomes when compared to culture-positive bacterial keratitis. Factors associated with poor outcome included diabetes, poor presenting VA, and positive cultures.

Traumatic superio-nasal subconjunctival dislocation of posterior chamber intraocular lens. A case report.

INTRODUCTION AND IMPORTANCE: Intraocular lens (IOL) implantation after cataract surgery is routine procedure. Traumatic dislocation of the posterior chamber IOL into the subconjunctival space following blunt ocular trauma is rare and it is considered an ophthalmic emergency. CASE PRESENTATION: We present a case of a 71-year-old male that presented to our institution with traumatic dislocation of a posterior chamber IOL into the superior-nasal subconjunctival space following blunt trauma to his left eye after an accidental fall on his head. DISCUSSION: Trauma in a pseduphakic eye can be devastating. Early recognition and treatment of IOL dislocation are of paramount importance to prevent further damage and infections. Half ring sign (Psudophacocele) recognition help in identifying and localizing the dislocated IOL in subconjunctival space. CONCLUSION: Traumatic dislocation of posterior chamber IOLs have been rarely reported in the literature. Nevertheless, it could happen years after implantation.

Assessment of the Levels of Knowledge Regarding Cataract and Glaucoma in Saudi Arabia and Measurement of the Ability to Differentiate Between the Two.

Objectives To assess the general public's level of knowledge on glaucoma and cataract and measure their ability to differentiate between the two. Materials and methods This was an analytic, cross-sectional study. We used a self-explanatory questionnaire to obtain information regarding the level of knowledge of glaucoma and cataract and measured the ability of the public to differentiate between the two in Saudi Arabia. The obtained results were manually entered into an Excel sheet and analyzed using the Statistical Package for the Social Sciences (SPSS) software version 26. Results The levels of knowledge on glaucoma and cataract and those of education were significantly associated (chi-square: P < 0.001). There was a significant association between having an eye condition and the ability to correctly define glaucoma and cataract (chi-square: P = 0.002). Concerning the definition of glaucoma, 48.4% of the participants who had a previous eye disorder answered correctly, whereas 40.1% of the participants who had no previous eye disorder answered correctly. In addition, 20.9% of the participants with a previous eye disease and 17.6% of the participants without any previous eye disease defined glaucoma incorrectly as cataract. A total of 71.4% of the participants with a previous eye disease, compared with 49.6% of the participants without any previous eye disease, correctly defined cataract. In addition, only 7.3% of the participants with a history of eye disease answered the definition of cataract as that of glaucoma (glaucoma: chi-square, P = 0.002; cataract: chi-square, P < 0.001). Conclusion This study is in line with other studies measuring the knowledge of the two diseases, with glaucoma being less known than cataract. While many of the participants were able to define glaucoma and cataract, they had many difficulties identifying how they present and which symptom belonged to cataract and glaucoma. Glaucoma and cataract were confused by a number of participants especially in the case of glaucoma as more defined it as cataract rather than the opposite.

Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case-control study.

OBJECTIVE: The genetic spectrum of primary open-angle glaucoma (POAG) in middle-eastern Saudi's is still elusive. To this end, we investigated an association between rs693421, rs2499601 and their haplotypes at chromosome 1q43 locus with POAG and its related clinical phenotypes. Genotyping was performed with TaqMan® assays. Haplotypes and their interaction analysis were carried out by SHEsis and SNPStats online tools. RESULTS: The minor "T" allele frequency of rs693421 was 0.48 in controls and 0.52 in cases (odds ratio (OR) = 1.15, 95% confidence interval (CI) 0.85-1.54, p = 0.368). Similarly, for rs2499601, the minor "C" allele frequency was 0.49 in controls as compared to 0.53 in cases (OR = 1.19, 95% CI 0.89-1.60, p = 0.236). Besides, genotype distribution for both these polymorphisms was also not significant in additive, dominant and recessive models. rs693421 and rs2499601, showed significant linkage disequilibrium (D' statistics = 0.69, p < 0.001) but haplotype association was non-significant (p = 0.698). The significance did not vary after adjustment to age and sex. No significant genotype association was observed with intraocular pressure, cup/disc ratio and number of anti-glaucoma medication in POAG group. Furthermore, age, sex and genotypes did not contribute any significant risk of POAG in regression analysis. We report no association between rs693421, rs2499601 and their haplotypes with POAG and related phenotypes.

Angiolipoma of the Orbit.

Angiolipoma is characteristically described as an encapsulated mass of mature adipose tissue containing clusters of small blood vessels. The authors have described an extremely rare case of angiolipoma of the orbit. This rare case is only the third reported in the orbit and should be readily recognized from other differential diagnoses. The patient had an excellent prognosis after full surgical excision.

Lack of Association between Variant rs7916697 in ATOH7 and Primary Open Angle Glaucoma in a Saudi Cohort.

A case-control genetic association study was performed to investigate whether variant rs7916697 in atonal bHLH transcription factor 7 (ATOH7), which has been previously reported to be associated with optic disc parameters and primary open angle glaucoma (POAG) in different ethnic groups, is a risk factor for POAG or any of its clinical phenotypes in a Saudi cohort. Genotyping of rs7916697 (G>A) variant was performed in 186 unrelated POAG cases and 171 unrelated nonglaucomatous controls of Saudi origin using real-time Taq-Man® assay. Genotypic and allelic association with POAG and its related clinical indices were evaluated. Demographic and systemic disease status did not differ significantly between POAG cases and controls. Association analysis between POAG cases and controls showed no significant genotype effect under additive (p=0.707), dominant (p=0.458), and recessive (p=0.554) models. Besides, the minor 'A' allele frequency was 0.39 in POAG cases and 0.36 in controls with no significant distribution (p=0.406). In addition, there was no significant difference between genotypes and clinical phenotypes such as intraocular pressure and cup/disc ratio within the POAG group, or any age and sex adjusted genotype effect on the disease outcome in regression analysis. Variant rs7916697 in ATOH7 is not associated with POAG or its clinical indices such as IOP and cup/disc ratio in a Saudi cohort.

Plexin domain containing 2 (PLXDC2) gene polymorphism rs7081455 may not influence POAG risk in a Saudi cohort.

OBJECTIVE: Plexin domain containing 2 (PLXDC2), a cell surface transmembrane protein receptor for pigment epithelium derived factor, is expressed in many tissues including the eye. Polymorphism rs7081455 flanking PLXDC2 has been associated with primary open angle glaucoma (POAG) and its clinical phenotypes and may have a role in POAG. Rs7081455 was genotyped in POAG cases (n = 188) and non-glaucomatous controls (n = 164) of Saudi origin using Taq-Man® to determine any association of this variant with POAG and its endophenotypes. RESULTS: The risk variant, 'G' allele, frequency was 0.56 and 0.52 in controls and POAG cases, respectively (p = 0.197) with was no significant deviation from Hardy-Weinberg equilibrium. Genotype analysis between cases and controls revealed no significant distribution under additive (p = 0.482), dominant (p = 0.590) and recessive models (p = 0.228). In addition, glaucoma specific phenotypic traits such as intraocular pressure (IOP) and cup/disc ratio; and number of anti-glaucoma medications, used to assess severity of the disease, were also statistically non-significant. Furthermore, regression analysis showed no significant effect of age, sex and genotype on disease outcome. Rs7081455 was not associated with POAG or its clinical phenotypes such as IOP and cup/disc ratio and hence may not be a significant risk factor for POAG patients of Saudi origin.

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.

Polymorphism rs10483727 in the SIX1/SIX6 Gene Locus Is a Risk Factor for Primary Open Angle Glaucoma in a Saudi Cohort.

AIMS: Variant rs10483727 in the SIX1/SIX6 locus has been significantly associated with primary open angle glaucoma (POAG) in multiple ethnic groups. We conducted a case-control study to investigate the association between this variant and POAG in a Saudi cohort. MATERIALS AND METHODS: Polymorphism rs10483727 was genotyped by using a TaqMan® assay in 186 subjects comprising 92 unrelated POAG cases and 94 controls all of Saudi origin. RESULTS: The "C" allele frequency was 0.33 and 0.45 among POAG cases and controls, respectively (odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.38-0.89; p = 0.013), suggesting a protective effect; and the "T" allele was associated with increased susceptibility to POAG (OR = 1.7, 95% CI = 1.11-2.58; p = 0.013). Genotype distribution was also significantly associated with POAG (χ2 = 6.41, df = 2, p = 0.041). Endophenotype traits such as intraocular pressure and cup/disk ratio did not show any significant genotype distribution in POAG cases. A binary logistic regression analysis used to evaluate the effects of age, gender, and genotype on the likelihood of having POAG showed that genotype distribution (p = 0.012) significantly affected the disease outcome as compared with age (p = 0.055) and sex (p = 0.432). CONCLUSION: The "T" allele of the rs10483727 polymorphism is an independent significant risk factor for POAG in the Saudi population.

Polymorphism rs13334190 in zinc finger protein 469 (ZNF469) is not a risk factor for keratoconus in a Saudi cohort.

OBJECTIVE: Polymorphism rs13334190 in the zinc finger protein 469 gene has been suggested to predispose toward a "thin" cornea, which then becomes keratoconic or is directly pathogenic. Thus, we genotyped polymorphism rs13334190 in 127 unrelated keratoconus cases and 168 control subjects from Saudi Arabia using Taq-Man® assay. RESULTS: The genotype frequency distribution did not deviate significantly from the Hardy-Weinberg equilibrium (p > 0.05). Overall, both the genotype and allele frequencies were not significantly different between cases and controls. A minor allele frequency of 0.068 was comparable to the aggregate rates ranging from 0.060 to 0.086 observed in other populations. Binary logistic regression analysis was performed to ascertain the effects of age, gender and genotype on the likelihood of having keratoconus. The analysis indicated that increased age was statistically significant (p = 0.000) and that females have a 2.19-fold increased risk (p = 0.018) of developing keratoconus. The genotype frequencies did not differ between the sporadic or familial keratoconus cases. Polymorphism rs13334190 is not an independent risk factor for keratoconus in the Saudi cohort.

Polymorphism rs11656696 in GAS7 Is Not Associated with Primary Open Angle Glaucoma in a Saudi Cohort.

AIMS: To conduct a case-control study to investigate the association between the polymorphism rs11656696 located in the growth arrest-specific 7 gene (GAS7)on human chromosome 17p13.1 and primary open angle glaucoma (POAG). METHODS: The polymorphism rs11656696 was genotyped using the TaqMan® assay in 187 subjects comprising 92 unrelated POAG cases and 95 controls of Saudi Arabian origin. RESULTS: Association analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.225), dominant (p = 0.635), or recessive (p = 0.085) models. Moreover, the allele frequency distribution was also nonsignificant (p = 0.70). The minor "A" allele frequency was 0.35 and 0.41 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disk ratio, and number of antiglaucoma medications also did not show any significant genotype distribution in POAG cases. Moreover, a binary logistic regression analysis did not show any significant effect of age, sex, or genotype on disease outcome. CONCLUSION: Polymorphism rs11656696 is not associated with POAG nor any of its endophenotypic traits such as IOP and cup/disk ratio and is thus not a risk factor for POAG in this Saudi cohort.

Polymorphism rs547984 on human chromosome 1q43 is not associated with primary open angle glaucoma in a Saudi cohort.

BACKGROUND: To investigate the association between polymorphism rs547984, located in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene on human chromosome 1q43 and primary open angle glaucoma (POAG). METHOD: Polymorphism rs547984 was genotyped using Taq-Man® assay in 185 subjects comprising of 90 unrelated POAG cases and 95 controls of Saudi origin. RESULTS: Association analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.356), dominant (p = 0.517) and recessive (p = 0.309) models. Besides, the allele frequency distribution was also found to be non-significant (p = 0.70). The minor "A" allele frequency was found to be 0.49 and 0.50 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medication also did not show any significant genotype distribution in POAG cases. CONCLUSION: Polymorphism rs547984 is neither associated with any clinical indices important for POAG such as IOP and cup/disc ratio nor is a risk factor for POAG in the Saudi cohort.

Lack of association between polymorphism rs540782 and primary open angle glaucoma in Saudi patients.

BACKGROUND: To investigate whether polymorphism rs540782 on chromsome 1, in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene, is a risk factor for primary open angle glaucoma (POAG). METHOD: The study genotyped 92 unrelated POAG cases and 95 control subjects from Saudi Arabia using Taq-Man® assay. RESULTS: The genotype frequency distribution did not deviate significantly from the Hardy-Weinberg equilibrium (p > 0.05). Overall, both the genotype and allele frequencies were not significantly different between cases and controls. The minor 'C' allele frequency was 49.4%, which was comparable to the Japanese population and higher than the Indian and Afro-Caribbean populations. Similarly, no significant association was found between genotypes and systemic diseases and health awareness/behavior domain variables. Importantly, glaucoma specific indices, such as intraocular pressure, cup/disc ratio and number of anti-glaucoma medication, also showed no statistically significant effect of genotypes within POAG cases. CONCLUSION: Polymorphism rs540782 is not a risk factor for POAG in the Saudi cohort.

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.