Association of single-nucleotide polymorphisms in non-coding regions of the TLR4 gene with primary open angle glaucoma in a Mexican population

Background: Toll-like receptor 4 (TLR4) non-coding polymorphisms are associated to primary open angle glaucoma (POAG), normal tension glaucoma, and pseudoexfoliation glaucoma. This study was performed to determine whether non-coding single nucleotide polymorphisms (SNPs) in the TLR4 gene contribute to POAG in a Mexican population.

Material and methods: A total of 187 unrelated Mexican patients with POAG and 109 control subjects were included. Allelic, genotypic, and haplotypic diversity was assessed for the non-coding polymorphisms rs11536889, rs1927911, rs12377632, and rs2149356 of the TLR4 gene. Genotyping of target SNPs was performed by 5′ exonuclease allelic discrimination assays.

Results: Strong linkage disequilibrium was observed among the SNPs (D’ > 0.818), which were located in one haplotype block. The rs11536889 polymorphism was not associated to POAG in any case. The frequency of the minor allele of rs2149356 was significantly higher in the glaucoma group, conferring an increased risk of POAG (p = 0.0018, OR = 1.803, 95% CI 1.2556–2.5890) whereas minor allele of rs12377632 was significantly lower, attributing a protective effect (p = 0.0001, OR = 0.6662, 95% CI 0.4753–0.9339). Subjects with genotypes carrying the minor allele of rs1927911 and rs2149356 shown an increased risk for POAG (p = 0.03, OR = 1.78, 95% CI 1.10–2.87, and p < 0.0004, OR =2.62, 95%CI 1.61–4.27 respectively). Finally, we found significant risk haplotypes. The GTT haplotype (constituted by rs1927911, rs12377632, and rs2149356) reached the higher OR (p = 0.0026, OR = 4.70, 95% CI 1.73–12.77).

Conclusions: We have identified intronic TLR4 SNPs as genetic susceptibility alleles for POAG in a Mexican population. Our findings support the association of the TLR4 gene with POAG.     

Juvenile Xanthogranuloma–A Rare Cause of Unilateral Orbital Swelling in an Elderly Patient

Objective: To report the clinical and pathologic features of an elderly patient with a unilateral orbital swelling and proptosis caused by Juvenile Xanthogranuloma diagnosed and confirmed by orbital biopsy.

Design: Interventional case report.

Participants: One patient.

Intervention: Steroids (Medrol dose pack) and radiation.

Main Outcome Measures: Unusual clinical presentation and pathological features of Juvenile Xanthogranuloma in the orbit.

Conclusions: Juvenile Xanthogranuloma affecting one orbit is very rare with unilateral involvement in an elderly patient. Steroids and radiation therapy were very effective in treatment and provided impressive results.     

Use of Aqueous Humor and Flow Cytometry in Ocular Sarcoidosis Diagnosis

Purpose: To report the use of flow cytometry on aqueous fluid to diagnose sarcoidosis in a patient with recurrent granulomatous anterior uveitis.

Methods: Case report.

Results: Flow cytometry on aqueous fluid demonstrated a CD4/CD8 ratio >9.5, consistent with a diagnosis of sarcoidosis.

Conclusions: Flow cytometry on aqueous fluid may offer an additional pathway for diagnosing sarcoid anterior uveitis.     

Giant Orbital Hydrocystoma in Children: Case Series and Review of the Literature

Objective: To describe the clinical features, ancillary diagnostic studies, and treatment outcomes in a cohort of pediatric patients with giant orbital hydrocystomas.

Design: Retrospective case series.

Participants: Pediatric patients with giant orbital hydrocystomas treated in the practice of one surgeon (PDL).

Methods: A retrospective review of the clinical charts of pediatric patients with orbital hydrocystoma was performed and diagnostic information collected. Results were reviewed and compared with reported clinical data in the literature.

Main Outcome Measures: Clinical presentation and histopathological findings of pediatric orbital hydrocystomas.

Results: Three pediatric cases of giant orbital hydrocystoma were encountered, each with an unusual feature, including deep orbital location, occurrence following trauma, and eccrine pathology.

Conclusion: Giant orbital hydrocystomas may present in the pediatric population. Ophthalmologists should be cognizant of this entity when evaluating a child with a large, cystic orbital mass.     

Investigating the CFH Gene Polymorphisms as a Risk Factor for Age-related Macular Degeneration in an Iranian Population

Background: Age-related macular degeneration (AMD) is a complex disorder which results in irreversible vision loss and progressive impairment of central vision. Disease susceptibility is influenced by multiple genetic and environmental factors. Single nucleotide polymorphisms (SNP) in the complement factor H gene are the most important genetic risk factors. We conducted a case-control study to investigate the association four SNPs (dbSNP ID: rs800292, rs1061170, rs2274700 and rs3753395) of CFH gene with AMD in the Iranian population.

Materials and Methods: We recruited 100 AMD patients and 100 age- and sex-matched normal controls. Direct sequencing for three SNPs (rs800292, rs2274700 and rs3753395) and restriction fragment length polymorphism utilized for rs1061170. Allele and genotype frequencies of SNPs were calculated and tested for departure from Hardy–Weinberg equilibrium using the Chi-square test. An allelic and genotypic association was compared by logistic regression analysis using the SNPassoc.

Results: According to our results, the frequencies of risk allele for all SNPs (G, G, A, and C alleles of rs800292, rs2274700, rs3753395 and rs1061170, respectively) were significantly higher in AMD patients (p value < 0.001). AMD individuals who had at least one copy of the C allele of rs1061170 had an increased risk of disease compared with cases with the T allele. Other studied polymorphisms showed the same association.

Conclusion: Our results suggest the contribution of all four predicted CFH polymorphisms in AMD susceptibility among the Iranian population. This association with CFH may lead to early detection and new strategies for prevention and treatment of AMD.     

Varicella Zoster-related Occlusive Retinal Vasculopathy—A Rare Presentation

Purpose: To report a case of occlusive retinal vasculopathy following varicella zoster infection in an immunocompetent adult.

Design: Observational case report.

Methods: A patient with defective vision following chickenpox was evaluated with fluorescein angiography, spectral domain optical coherence tomography and fundus auto fluorescence.

Results: Fundus showed multiple cotton wool spots and a well-demarcated zone of retinal ischemia in the posterior pole with normal optic disc without any evidence of anterior or posterior uveitis. Fluorescein angiography, spectral domain optical coherence tomography and fundus auto fluorescence findings revealed occlusive vasculopathy as the cause of defective vision.

Conclusions: We report a hitherto undescribed case of purely occlusive vasculopathy following varicella zoster infection without features of vasculitis or anterior and posterior uveitis in an immunocompetent individual.     

ENOS polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Chinese Han population

Purpose: To investigate whether common genetic variants in the endothelial nitric oxide synthase gene (eNOS) are associated with neovascular age-related macular degeneration (nAMD) and polypoidal choroidalvasculopathy (PCV) in a Chinese Han population.

Methods: DNA samples were obtained from 157 nAMD patients, 250 PCV patients and 204 healthy control subjects. Tag single nucleotide polymorphisms (SNPs) across the extended eNOS region were selected using data derived from the HapMap project. Genotyping of each tag SNP was performed by Multiplex SNaPshot system and direct DNA sequencing techniques. Genotypes and allele frequencies were evaluated with PLINK software for each group.

Results: Seven SNPs for eNOS, rs1799983, rs1800783, rs3918186, rs3800787, rs3918188, rs7830, and rs3918227, were chosen as tag SNPs. Among these tag SNPs, rs1800783, rs3918186, rs3918188, and rs3918227 were not associated with nAMD or PCV. Rs1799983, rs3800787, and rs7830 was significantly associated with nAMD (p = 0.0192, 0.0170, and 0.0164, respectively), but not associated with PCV (p = 0.4852, 0.4568, and 0.4014, respectively). The discovered associations were no longer significant after Bonferroni correction.

Conclusions: We found no sufficient evidence to support the role of any common eNOS variants in the susceptibility to nAMD or PCV in a Chinese Han population.     

Retinal capillaritis in a CRB1-associated retinal dystrophy

Purpose: To report a case of CRB1-associated retinal dystrophy characterized by vitritis, retinal capillaritis, and cystoid macular edema (CME).

Methods: A case report.

Results: An 8-year-old boy was diagnosed with intermediate uveitis and treated with corticosteroids. He was subsequently diagnosed with retinal dystrophy and found to have two CRB1 mutations.

Conclusions: Retinal capillaritis, vitritis, and CME could be inflammatory features of CRB1 retinal dystrophy in our young patient.     

Dengue Fever Presenting as Purtscher-like Retinopathy

Purpose: To report the fundus manifestations and spectral-domain optical coherence tomographic (SD-OCT) features of dengue fever presenting as Purtscher-like retinopathy.

Methods: Retrospective review of two cases of dengue fever.

Results: Color fundus photograph revealed the presence of cotton-wool spots in a Purtscher-like configuration in the posterior pole of all study eyes. SD-OCT demonstrated increased reflectivity signal in the inner retinal layers, and after a variable follow-up period, there was complete disappearance of cotton-wool spots and persistence of the hyperreflectivity signal.

Conclusion: We report two unique cases of dengue fever associated with retinal lesions in a configuration of Purtscher-like retinopathy.     

Clinical and genetic characterization of a large primary open angle glaucoma pedigree

Purpose: To both characterize the clinical features of large primary open angle glaucoma (POAG) pedigree from a village in southern India and to investigate the genetic basis of their disease.

Materials and methods: Eighty-four members of a large pedigree received complete eye examinations including slit lamp examination, tonometry, gonioscopy, and ophthalmoscopy. Some were further studied with perimetry. Those diagnosed with POAG were tested for disease-causing mutations in the myocilin and optineurin genes with Sanger sequencing.

Results: Fourteen of 84 family members were diagnosed with POAG, while eight were clinically judged to be POAG-suspects. The family structure and the pattern of glaucoma in the pedigree are complex. Features of glaucoma in this pedigree include relatively early age at diagnosis (mean 50 ± 14 years) and maximum intraocular pressures ranging from 14 to 36 mm Hg with a mean of 23 mm Hg ± 6.5 mm Hg. Patients had an average central corneal thickness (mean 529 ± 37.8 microns) and moderate cup-to-disc ratios (0.74 ± 0.14). No mutations were detected in myocilin, optineurin, or TANK binding kinase 1 (TBK1).

Conclusions: We report a five-generation pedigree with a complex pattern of POAG inheritance that includes 22 POAG patients and glaucoma suspects. Although the familial clustering of POAG in this pedigree is consistent with dominant inheritance of a glaucoma-causing gene, mutations were not detected in genes previously associated with autosomal dominant glaucoma, suggesting the involvement of a novel disease-causing gene in this pedigree.     

MYOC Mutations in Black South African Patients with Primary Open-angle Glaucoma: Genetic Testing and Cascade Screening

Background: Primary Open Angle Glaucoma (POAG) is an important cause of irreversible blindness in South Africa. Mutations in the MYOC gene are important in monogenic POAG. This study aimed to characterize potentially pathogenic MYOC mutations in this population.

Materials and Methods: Self-identified black South African POAG patients (215) and unaffected control participants (214) had ophthalmological examinations and DNA extraction. Potentially pathogenic MYOC variants were genotyped in the study population. Family members of participants with the mutations were screened for glaucoma clinically and for the mutations using Sanger sequencing.

Results: The following mutations were genotyped: Gly374Val (2 POAG patients), Lys500Arg (3 POAG patients) and Tyr453del (5 POAG patients). None of the relatives screened for Gly374Val had the mutation or POAG. The Lys500Arg mutation did not co-segregate with the disease in an affected family. The Tyr453del mutation co-segregated with the disease, but demonstrated incomplete penetrance. POAG patients with the Tyr453del mutation had adult-onset POAG with high intraocular pressures and advanced cupping.

Conclusions: Overall, 3.3% of black South Africans with POAG have a Gly374Val or Tyr453del MYOC mutation. The Tyr453del mutation is incompletely penetrant. That the mutation is necessary but insufficient introduces a counseling dilemma. Mutation screening can, however, identify high-risk individuals who can be monitored to detect early signs of the disease. The Gly374Val mutation is predicted to be damaging to MYOC. The Lys500Arg mutation is predicted to be benign and tolerated. This study has important implications for the management and counseling of black South African patients with POAG and their families.     

Analysis of toll-like receptor rs4986790 polymorphism in Saudi patients with primary open angle glaucoma

Background: To investigate whether SNP rs4986790 in toll-like receptors (TLRs) is a risk factor for primary open angle glaucoma (POAG) in a Saudi population.

Materials and methods: A cohort of 85 unrelated POAG patients and 95 unrelated control subjects from Saudi Arabia were genotyped utilizing Taq-Man® assay. The association between mutant genotypes and various clinical indices important for POAG was investigated.

Results: Among cases, the normal pattern (A/A) was detected in 70 (82.4%) of the subjects, A/G in 14 (16.5%) and G/G in one subject only (1.2%). Among controls, prevalence of the genotype (A/A) was detected in 86 (90.5%), the (A/G) genotype in 8 (8.4%) and homozygous mutated genotype (G/G) in 1 (1.1%) subjects. Comparing cases to controls, the odds ratio of having heterozygous mutation (A/G) was 2.15 [95% CI: 0.853–5.417], which was not significant (p = 0.114). The odds ratio of having homozygous mutation (G/G) was 1.22 [95% CI: 0.075–19.99], which was statistically non-significant (p = 0.568). Likewise, the presence of the mutated allele (G) was non-significantly different between cases and controls (p = 0.154). Comparing cases to controls as regards co-morbidity with other systemic diseases, there were no statistically significant differences between groups in all assessed diseases except for a family history of glaucoma (p = 0.014)

Conclusions: In conclusion, we could not detect any direct link between genotypes or allele frequencies of SNP rs4986790 in the TLR4 gene and POAG. In contrast, genotype (A/A) may be protective against POAG especially among individuals with no family history of glaucoma.     

Enucleation Refusal for Retinoblastoma: A Global Study

Background: Enucleation (eye removal) is often the only curative treatment for the childhood eye cancer retinoblastoma, yet parental refusal of enucleation commonly contributes to treatment delay and poor survival globally.

Methods: Physicians who treat retinoblastoma were surveyed to glean underlying reasons for treatment refusal.

Results: Refusal rates were higher when less time was spent with parents explaining retinoblastoma/enucleation, and where fewer support services were available. Reasons for refusal included parental belief in alternative treatments, culture, and social stigma.

Conclusions: We suggest strategies to increase parental compliance with enucleation and save the lives of children with retinoblastoma.     

Macular hole in Stargardt disease: Clinical and ultra-structural observation

Purpose: To report for the first time a case report of a Stargardt disease patient who developed a macular hole (MH) which was treated with a surgical approach.

Method: Case report.

Results: After vitrectomy a complete closure of the MH was obtained and the best-corrected visual acuity remained stable. No complications were reported after one year of follow-up. An ultra-structural examination of the removed internal limiting membrane (ILM) and epiretinal membrane (ERM) was carried out under electron microscopy.

Conclusion: Vitreo-retinal surgery could represent a therapeutic option to treat vitreo-retinal interface abnormalities associated with inherited retinal diseases.     

Evaluating VEGFR1 genetic polymorphisms as a predisposition to AMD in a cohort from northern China

Objective: The association among genetic variants in VEGFR1 and a predisposition to age-related macular degeneration (AMD) in a northern cohort from China was evaluated.

Methods: A retrospective case-control correlation study was conducted on 432 cases and 906 gender-and ethnicity-matched controls. Whole DNA was isolated from peripheral blood samples after the individuals underwent detailed eye examinations. Eight single nucleotide polymorphisms (SNPs) in VEGFR1 genes were genotyped for all individuals using a MALDI-TOF technique. The distribution of genotypes was analyzed for Hardy-Weinberg equilibrium and the relationships among the genotype and allele frequencies with AMD were evaluated by age-adjusted logistic regression analysis. The measurement of linkage disequilibrium (LD) was carried out by Haploview 4.2. Bonferroni testing was employed to correct for multiple comparisons.

Results: Among the SNPs genotyped, p values of six SNPs were less than 0.05 between AMD cases and unaffected controls. However, after Bonferroni correction, the genotype and allele distributions of only two SNPs, rs9554322 and rs9582036 differed significantly between the controls and AMD patients. Further, the rs9554322 CC genotype conferred strong susceptibility to AMD (OR = 6.057, 95% CI: 3.099–11.839). Rs9943922 was also found to be significantly associated with AMD in the distributions for the genotype and allele recessive model (p = 0.004). The specific haplotype CA of rs9582036 and rs9554320 was associated with AMD (p = 0.035), but the correlation did not remain after correction.

Conclusions: The SNPs rs9554322, rs9582036 and rs9943922 were correlated with AMD. Gene variants in VEGFR1 were linked to a pronounced emerging risk for AMD in a population in northern China.     

Genetic factors influencing the reduction of central corneal thickness in disorders affecting the eye

Background: The aim was to summarize and discuss the current knowledge about genetic factors influencing the reduction of central corneal thickness (CCT) in disorders affecting the eye, such as primary open-angle glaucoma (POAG), brittle cornea syndrome (BCS), keratoconus (KTCN), Ehlers–Danlos syndrome (EDS; types I, II, and VI), osteogenesis imperfecta (OI), and myopia.

Materials and methods: A review of the published literature by use of key databases such as PubMed was undertaken in accordance with PRISMA guidelines and experience based on own research findings was applied.

Results: The differences in CCT measurements among those affected with diverse disorders and healthy individuals were evaluated. Then we considered the influence of genetic factors on CCT reduction. Disorders were compared based on phenotypes and sequence variants found in patients.

Conclusions: Specific sequence variants in COL8A2, PRDM5 and ZNF469, COL5A1 and ZNF469, and COL5A1 and COL5A2 could probably contribute to a CCT reduction in POAG, BCS, KTCN, and EDS, respectively. Similar sequence variants and phenotypes were identified and assessed in more than one disease.     

A Hemophagocytic Lymphohistiocytosis Patient that Presented with Unilateral Panuveitis

Purpose: To describe a case of hemophagocytic lymphohistiocytosis (HLH) with ocular changes prior to the systemic changes.

Methods: A 53-year-old man presented with the chief complaint of decreased vision in his right eye. The patient was examined by ocular examination, slit lamp examination, optical coherence tomography, laboratory examination, abdominal ultrasound, and bone marrow biopsy.

Results: Ocular examination revealed uveitis OD and optical coherence tomography revealed macular edema OD. Laboratory examination demonstrated cytopenia in two cell lines, hypofibrinogenemia, and elevated serum ferritin. Abdominal ultrasound findings indicated hepatosplenomegaly. The bone marrow biopsy specimen demonstrated histiocytes and significant hemophagocytosis, leading to a diagnosis of HLH.

Conclusion: Ophthalmic manifestation can be the first sign of HLH and progress to fatal systemic changes.     

Undiagnosed Primary Open-Angle Glaucoma in Korea: The Korean National Health and Nutrition Examination Survey 2008–2009

Purpose: To evaluate the characteristics of patients with previously undiagnosed primary open-angle glaucoma (POAG) in Korea.

Methods: This study examined data from 391 subjects obtained from the 2008–2009 Korean National Health and Nutrition Examination Survey (KNHANES). The KNHANES is a population-based, cross-sectional epidemiological survey. Participants aged 19 years or older completed standardized interviews and dilated ocular examinations, including measurement of intraocular pressure, visual fields with frequency doubling perimetry, and fundus photography. Data from the 361 patients with previously undiagnosed POAG were analyzed and compared with data from the 30 patients with previously diagnosed glaucoma.

Results: A total of 92.3% of POAG cases were undiagnosed before this study. Adjusted for age and sex, the strongest risk factor for undiagnosed glaucoma was longer elapsed time since last eye doctor visit. Glaucoma patients who had not visited an eye specialist in the last 3 years were 22 times (95% confidence interval, CI, 4.49–105.64, p < 0.001) more likely to have undiagnosed disease compared with patients who had visited an eye specialist in the last month. Another significant factor for previously undiagnosed glaucoma was smaller cup-to-disc ratio (odds ratio, OR, 0.60/0.1 units, 95% CI 0.43–0.85/0.1 units, p = 0.004). The higher vertical cup-to-disc ratio of a subject’s two eyes was significantly different between those with previously undiagnosed (0.69) and diagnosed (0.78) POAG (p = 0.001).

Conclusions: The undiagnosed POAG group had a longer interval from last eye doctor visit and smaller vertical cup-to-disc ratio compared to the diagnosed group.     

Sepsis During Immunosuppression for Sight-threatening Uveitis: The Flip side

Purpose: To highlight the rare but life-threatening infective consequences of immunosuppression or biologic treatment for sight-threatening uveitis.

Patients and methods: Retrospective case series of four immunosuppressed patients with uveitis complicated by sepsis.

Results: The affected patients were all treated using prednisolone 10 mg/day or greater, together with oral immunosuppression (2 mycophenolate mofetil, 1 azathioprine + ciclosporin, 1 methotrexate) and, in one case, infliximab. All patients survived following intensive treatment.

Conclusion: Life-threatening infection is a rare but important risk in immunosuppressed patients with uveitis. Complete protection is not possible and prophylaxis regimens are of unproven efficacy. Patients should understand the risks before agreeing to a course of treatment.     

Punctal Ectropion repair using the Raus–Garito clamp

Purpose: To evaluate the results from the correction of ectropion of the punctum lacrimale in lower eyelids with a new surgical clamp.

Design: Prospective study.

Methods: Eighty eight eyelids in 55 patients with mild and moderate ectropion were included in the study. An excision of a diamond of tarso-conjunctiva with retractor reattachment and concomitant correction of horizontal lid laxity, if present, was performed.

Results: Resolution of tearing was obtained in 77 eyes. In 11 eyes, persistent tearing was reported.

Conclusion: Conclusion:Conclusion: Repair of early to intermediate ectropion of the lacrimal punctum using the Raus–Garito clamp is associated with a good functional and cosmetic outcome.