Impact of rs11024102 PLEKHA7, rs3753841 COL11A1 single nucleotide polymorphisms, and serum levels of oxidative stress markers on the risk of primary angle-closure glaucoma in Egyptians.

BACKGROUND: Primary angle-closure glaucoma (PACG) is one of the major causes of blindness in the Middle East with genetic loci and systemic oxidative stress as potential risk factors. The current case-control study aimed to investigate the associations of rs11024102 in Pleckstrin homology domain-containing family A member 7 (PLEKHA7), rs3753841 in collagen 11 A1 (COL11A1), and the systemic oxidative stress markers with PACG in Egyptian patients. Thirty-five control subjects and 64 PACG patients were enrolled in this study. The polymorphisms in PLEKHA7 and COL11A1 were analyzed using quantitative PCR, and their associations were statistically tested with PACG at homozygous, heterozygous, dominant, and recessive genetic models. The levels of malondialdehyde (MDA), advanced glycation-end product (AOPP), protein carbonyl (PC), and ischemia modified albumin (IMA) were quantitated colorimetrically, and their associations with PACG were analyzed statistically. The associations of MDA, AOPP, PC, and IMA with elevated intraocular pressure (IOP) were statistically tested. RESULTS: Neither significant difference in the genotype distribution nor allele frequency of PLEKHA7 11024102 T>C (p = 0.425 and 0.517, respectively) and COL11A1 rs3753841 G>A (p = 0.600 and 0.473, respectively) were recorded under any of the tested genetic models. Either rs11024102 PLEKHA7 or rs3753841 COL11A1 was not significantly (p > 0.025 after Bonferroni correction) associated with an increased risk of PACG in Egyptians. Egyptian patients with PACG showed significant elevations in the serum levels of MDA, AOPP, and PC either in patients with or without cases with diabetes mellites, hypertension, coronary vascular diseases, and smoking. Serum levels of MDA, AOPP, and PC were significantly associated with PACG in Egyptians (p < 0.013 after Bonferroni correction). However, MDA and PC only showed significant associations with the elevation in the IOP (p = 0.007 and 0.045, respectively) in PACG patients. CONCLUSION: Both rs11024102 and rs3753841 could not be considered as potential gene-dependent risk factors for PACG pathogenesis in Egyptians. On the other hand, serum levels of MDA, AOPP, and PC might be considered risk factors for PACG. Moreover, MDA and PC could serve as good predictors for the elevation of the IOP in PACG disease.

Long-Term Effect of Early Phacoemulsification in Primary Angle Closure Glaucoma Patients with Cataract: A 10-Year Follow-Up Study.

PURPOSE: To assess the 10-year effects of early phacoemulsification with intraocular lens (IOL) implantation in primary angle closure glaucoma (PACG) patients with cataract. PATIENTS AND METHODS: This prospective cohort study included 102 eyes of 102 patients with PACG. All patients had coexisting cataracts compromising vision. Patients underwent phacoemulsification and foldable IOL implantation. The main outcome measures were anterior chamber depth (ACD), angle width, value of intraocular pressure (IOP), and number of medications needed postoperatively and during follow-up. RESULTS: Half (53%) of the patients were female, with ages ranging from 55 to 73 with a mean of 59.82±5.19 years. Mean IOP decreased significantly from 22.15±2.08 mmHg at baseline to 14.08±2.13 mmHg postoperatively (p˂ 0.05). The ACD increased from 2.2±0.21 preoperatively to 3.73±0.25 postoperatively (p˂0.001). Nasal angle width increased postoperatively to 40.05±2.09 compared to the preoperative value of 16.02±2.08 (p˂0.001). Temporal angle width increased from 13.05±2.07 to 41.9600±1.94 (p˂0.001). Anti-glaucoma treatment significantly decreased postoperatively (p˂0.001). A significant positive correlation was detected between ACD and angle width, while a negative correlation was detected between IOP and both ACD and angle width (p˂0.001). There was also a significant negative correlation between postoperative angle width and IOP (p˂0.001). Preoperative lens thickness was positively correlated with preoperative IOP and number of medications, while it was negatively correlated with preoperative AC depth and angle width. Preoperative lens thickness positively correlated with postoperative IOP and medications. Complete and qualified success was achieved in 69.65% and 30.4% of cases, respectively, while 2.9% failed to be controlled. Visual acuity significantly improved from 0.17±0.1 to 0.9±0.08 (p˂0.001). All parameters showed high stability throughout the follow-up period. CONCLUSION: Phacoemulsification with IOL implantation is a safe and effective early modality for long-term control of IOP in PACG patients with coexisting cataract. The effects can persist for at least 10 years.

Ab Interno Goniotomy Combined with Ab Externo Trabeculotomy in Advanced Primary Congenital Glaucoma Patients: 2-Year Follow-Up.

INTRODUCTION: Primary congenital glaucoma (PCG) is a challenging disease that needs to be surgically managed with more innovative methods. Conventional incisional surgery, such as goniotomy and trabeculotomy, has a primary high success rate, but does not seem to be a very effective treatment in advanced stages. DESIGN: A prospective clinical case study. PURPOSE: To qualify the outcome, in terms of success rate, of goniotomy combined with trabeculotomy as a surgical option to treat eyes affected by PCG with a corneal diameter larger than 14 mm. PATIENTS AND METHODS: This study included 50 eyes of 50 patients diagnosed with PCG with corneal diameter larger than 14 mm who underwent ab interno goniotomy combined with ab externo trabeculotomy. Intraocular pressure (IOP) was measured preoperatively and 24 months postoperatively. A statistical analysis was performed to detect correlations between the success rate and corneal diameter, preoperative IOP, age of onset, axial length, and consanguinity. The main outcome was reduction in IOP; secondary outcomes were factors affecting the success rate, complications, and the need for additional surgical intervention to control IOP. RESULTS: The mean age of the patients was 18.86±9.94 months. Males made up 52% of cases and females 48% of cases. Positive consanguinity was present in 38% of cases. Axial length ranged between 20 and 22 mm, with a mean of 20.98±0.8 mm. Mean preoperative IOP was 29.56±3.36 mmHg, which decreased postoperatively to 12.6±2.5, 14.1±3.2, 16.8±5.5, 14.4±2.3, 14.3±1.6, 14.3±1.6, 14.3±1.6, 14.3±1.7, and 14.3±1.7 mmHg at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months respectively (p˂0.001). Use of medical treatment was decreased from 2.7±0.4 preoperatively to 1.4±0.7 postoperatively (p˂0.001). Hyphema was the only complication that appeared, occurring in 47% of cases. The success rate was 94%. Complete success (IOP <21 mmHg without treatment) was achieved in 70% of cases, 24% were considered a qualified success (IOP <21 mmHg with treatment), while failure was documented in 6% of cases (IOP >21 mmHg with treatment). The success rate was significantly related to preoperative IOP, corneal diameter, axial length, consanguinity, and age of onset (p˂0.001). All cases were followed for 24 months. CONCLUSION: Ab interno goniotomy combined with ab externo trabeculotomy improves the success rate of buphthalmos surgery. A significant correlation was detected between success rate and preoperative IOP, corneal diameter, axial length, consanguinity, and age of onset.

Intraocular Pressure Calculation in Myopic Patients After Laser-Assisted In Situ Keratomileusis.

BACKGROUND: Corneal refractive surgery is widely used worldwide. Myopia is the most common reason for laser-assisted corneal refractive surgery (LASIK) and one of the risk factors for glaucoma. Intraocular pressure (IOP) measurement becomes variable postoperatively as the results are affected by the decrease in corneal thickness and biomechanics. This prospective clinical case study attempted to establish a simple correction formula for the calculation of IOP in post-LASIK myopic patients. METHODS: This study included 300 eyes of 150 patients with myopia and myopic astigmatism as a refractive error who underwent LASIK. IOP was measured preoperatively and 6 months postoperatively. Preoperative and postoperative corneal thickness as well as ablation depth were measured. Statistical analysis was performed to detect the relationship between ablation depth and change in IOP. An attempt was made to construct a correction formula for the calculation of post-LASIK IOP. RESULTS: The age of the patients ranged between 18 and 50 (mean ± SD 34.78±8.8) years. The spherical equivalent of refractive error ranged between -1.5 and -10 diopters. The mean IOP decreased significantly from 15.72±2.37 mmHg preoperatively to 11.71±2.24 mmHg postoperatively, with a mean difference of 4±1.75 mmHg (p˂0.001). A positive correlation was detected between corneal thickness and IOP difference among patients both preoperatively and postoperatively (p˂0.001). A positive correlation was identified between ablation depth and IOP change (p˂0.001). The correction formula for IOP was established: Real IOP=4+0.7(preoperative IOP)-0.3(ablation depth). CONCLUSION: IOP measurements change after corneal refractive surgery with LASIK. A corrected formula may be a good option for the proper calculation of post-LASIK IOP.

Role of Angiopoietins and Tie-2 in Diabetic Retinopathy.

OBJECTIVE: The aim of this study was to determine the serum levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble vascular endothelial tyrosine kinase receptor (Tie-2) and vascular endothelial growth factor (VEGF), in the serum of type 2 diabetic patients having non-proliferative (NPDR) or proliferative diabetic retinopathy (PDR). METHODS: One hundred patients with type 2 diabetes mellitus were involved in this cross-sectional study. They were classified into 25 diabetic patients without retinopathy, 35 patients with NPDR and 40 PDR patients. The study was carried out in the outpatients clinic of the Research Institute of Ophthalmology, Giza, Egypt from August 2016 through May 2017. Serum VEGF, Ang-1, Ang-2 and Tie-2 receptor levels were assayed using enzyme linked immunosorbent assay (ELISA). Data were analyzed by SPSS version 20 and Microsoft Excel (Version 10) using ANOVA, Harman's single factor test, and Pearson's Product Moment Correlation. RESULTS: The serum levels of Ang-2 and VEGF were significantly elevated in NPDR groups and PDR group compared to diabetics without retinopathy groups (p<0.001). The serum levels of Ang-1 were significantly higher in the NPDR group compared to the diabetics without retinopathy groups (p<0.01), while no significant difference was observed between the PDR and diabetics without retinopathy groups. Ang-1/Ang-2 ratio was the lowest in the PDR group compared to the NPDR and diabetics without retinopathy groups. The serum levels of Tie-2 were not significantly changed among the three studied groups, serum Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups. CONCLUSION: The angiopoietin/Tie system and VEGF are essential features in the commencement and development of PDR.

Levels of cytokines in the aqueous humor of eyes with primary open angle glaucoma, pseudoexfoliation glaucoma and cataract.

OBJECTIVE: The focus of this study aimed at measuring multiple inflammatory cytokines levels in the aqueous humor of patients with primary open angle glaucoma (POAG), pseudoexfoliation glaucoma (PEXG) and senile cataract. METHODS: This case control study was conducted at the Research Institute of Ophthalmology, Giza, Egypt in 2016. Aqueous humor (AH) samples were withdrawn from 50 patients (30 POAG, and 20 PEXG) and from 15 patients with senile cataract serving as controls. The levels of IL6, IL8, transforming growth factor ß1 (TGFß1), tumor necrosis growth factor α (TNFα) and serum amyloid A (SAA) were analyzed by ELISA immune-assay. Data were analyzed by SPSS 10, using Pearson Product-Moment Correlation and independent-samples t-test. RESULTS: The levels of IL8, TGFß1, TNFα and SAA were significantly higher in POAG and PEXG patients, compared to senile cataract patients. While the levels of IL6, were significantly decreased in both groups of glaucoma patients compared to cataract patients. Significant positive correlations were detected between IL6, IL 8 & TGF ß1, IL 8; SAA, IL8 & TGFß1, SAA in the aqueous humor of different groups. CONCLUSION: Thus the assayed cytokines including TGFß1, TNFα, IL8 and SAA in aqueous humor, play a vital role in IOP elevations in patients with POAG and PEXG.

Aggressive Recurrence of Primary Hepatic Epithelioid Haemangioendothelioma after Liver Transplantation.

HEHE is a rare neoplasm of vascular origin that occurs in the liver; UNOS reported a favorable outcome after liver transplantation in 110 patients with 1-year and 5-year survival of 80% and 64%. Case Report. A 40-year-old lady presented with a three-month history of right upper abdominal pain with nausea, vomiting, and significant loss of weight associated with scleral icterus and progressive abdominal distension. Examination revealed jaundice, hepatomegaly, and ascites. Serum bilirubin was 26.5 mg/dL and ALP was 552 CT. Abdomen and pelvis showed diffuse infiltrative neoplastic process of the liver with a mass effect and stretching of the hepatic and portal veins, in addition to bile duct dilatation. Viral hepatitis markers were negative and serum alpha fetoprotein was within reference range. Liver biopsy was consistent with HEHE, with positive endothelial markers (CD31, CD34, and factor VIII-related antigen). She underwent living related liver transplantation on June 2013 and was discharged after 20 days with normal liver enzymes. Four months later, she presented with diffuse disease recurrence. Liver biopsy confirmed disease recurrence; she received supportive treatment and unfortunately she died 2 weeks later. Conclusion. HEHE can have rapid and aggressive recurrence after liver transplantation.

Phacoemulsification combined with deep sclerectomy augmented with mitomycin and amniotic membrane implantation in chronic primary open angle glaucoma with cataract.

OBJECTIVE: The aim of this study was to determine the safety and efficacy of combined phacoemulsification plus Intraocular lens (IOL) implantation with deep sclerectomy augmented with mitomycin C (MMC) and sub-flap implantation of amniotic membrane for the management of uncontrolled, chronic, primary open-angle glaucoma patients. METHODS: This prospective study included 41 patients with chronic, primary, open-angle glaucoma and cataract uncontrolled with medical treatment who underwent combined phacoemulsification augmented with mitomycin C (MMC) application and amniotic membrane implantation under the scleral flap. Intraocular pressure (IOP), visual acuity, glaucoma medications, stabilization of visual field, complications, and viability of the success rate were assessed a 36-month follow-up period. RESULTS: The mean age of cases was 54.8 ± 5.3 years. Sixty-one percent of cases were males, and 39% were females. The mean IOP decreased from 23.8 ± 1.8 mmHg preoperatively to 16.8 ± 2.3 mmHg postoperatively. The overall success rate was 97.5, 95, and 92.7% in the first, second, and third year, respectively. The overall success rate was 90% in the first year, but that decreased to 85.3 and 78% in the second and third year, respectively. Qualified success was 7.5, 10, and 14.7% in the first, second, and third year, respectively. Failure was recorded as 2.5, 5, and 7.3% in the first, second, and third year, respectively. IOP reduction was sustained through the follow-up period. Visual acuity improved from 0.13 ± 0.06 to 0.9 ± 0.07 (p < 0.001). The visual field improved significantly in the first assessment, from 14.0 ± 2.7 preoperatively to 12.6 ± 2.6 at three months postoperatively (p < 0.001), after which it became stable for the remainder of the follow-up period. One hundred percent of cases were on three anti-glaucoma drugs preoperatively, while postoperatively, 12.2% were on three drugs, 4.2% were on two drugs, and 82.9% were controlled without anti-glaucoma treatment. There were minor postoperative complications all of which were minor, such as a spike in the post-operative IOP and the formation of fibrinous material in the anterior chamber, both of which were treated medically without any adverse effects on the final results. CONCLUSION: Amniotic membrane implantation in conjunction with MMC application may be an effective alternative to expensive implants in deep sclerectomy combined with phacoemulsification, and this approach can be used safely in advanced cases.

Corneal biomechanics in asymmetrical normal-tension glaucoma.

PURPOSE: We aimed to assess corneal biomechanics using the ocular response analyzer in patients with normal-tension glaucoma (NTG), and to evaluate the relationship between corneal biomechanics and visual field loss. METHODS: This was a prospective observational case series including patients with bilateral asymmetric NTG. For all patients, corneal hysteresis (CH), corneal resistance factor (CRF), CH - CRF difference, and central corneal thickness values were matched against the mean deviation (MD) of the visual field and the cup/disc ratio. For paired-eye comparison in each patient, both eyes were categorized into a better-eyes group and a worse-eyes group according to lower and higher corneal-compensated intraocular pressure readings, respectively. Statistical analysis was carried out with the independent-samples Student's t-test, and the level of statistical significance was set at 0.05. Correlation was assessed using Pearson's correlation coefficient. RESULTS: The study included 240 eyes of 120 patients. CH was inversely proportional to the MD in the visual field (P=0.01). CRF in both eyes was inversely proportional to the MD of the visual field (P=0.01). CH - CRF difference was directly proportional to the MD of the visual field (P=0.01). For paired-eye comparison, lower corneal-compensated intraocular pressure was associated with higher CH, higher CRF, smaller cup/disc ratio, and less deterioration of MD of visual field. CONCLUSION: CH, CRF, and CH - CRF are more powerful predictors of NTG progression than central corneal thickness.

Combined trabeculotomy-trabeculectomy versus Ahmed valve implantation for refractory primary congenital glaucoma in Egyptian patients: a long-term follow-up.

INTRODUCTION: Primary congenital glaucoma (PCG) is the most common type of glaucoma in pediatric patients. The aim of this study was to compare the effectiveness of combined trabeculotomy-trabeculectomy versus Ahmed valve implantation for cases of PCG refractory to traditional incisional angle surgery (goniotomy and trabeculotomy) in the Egyptian population. METHODS: The study was conducted in the Glaucoma Clinic of the Research Institute of Ophthalmology (Egypt). The study included 66 eyes of 66 patients (in two groups) with advanced PCG who had previous failed goniotomy, trabeculotomy, or both. Group 1 included 33 patients who underwent trabeculotomy-trabeculectomy procedures; group 2 included 33 patients who underwent FP 8 Ahmed valve implantation. The main outcome measures were intraocular pressure (IOP) reduction, corneal diameter, and axial length stability in both groups. Secondary outcome measures included detection of complications in both groups. RESULTS: The average ages of the patients were 13.5 ± 3.9 months and 15.3 ± 5.8 months in groups 1 and 2, respectively. Ten patients (30.3%) in group 1 and 9 patients (27.3%) in group 2 had family histories of PCG. Positive consanguinity was present in 26 patients (78.8%) in group 1 and in 27 patients (81.8%) in group 2. In group 1, the mean intraocular pressure (IOP) value decreased from 33.6 ± 3.4 mmHg preoperatively to 13.8 ± 0.6, 16.9 ± 1.5, 18.2 ± 2.5, 19.8 ± 3.6, and 20.2 ± 3.1 mmHg in the first postoperative month and after years 1, 2, 3, and 4, respectively (p < 0.001). In group 2, the mean IOP value decreased from 33.4 ± 4.5 mmHg preoperatively to 13.3 ± 1.1, 16.3 ± 1.6, 18.1 ± 1.0, 19.1 ± 3.5, and 19.9 ± 3.7 mmHg in the first postoperative month and after years 1, 2, 3, and 4, respectively (p < 0.001). The average number of medications decreased from 2.2 ± 0.4 preoperatively to 1.8 ± 0.4 postoperatively in group 1, while it decreased from 2.1 ± 0.4 preoperatively to 1.9 ± 0.3 postoperatively in group 2. The success rate in group 1 was 97, 91, 76, and 61% in years 1, 2, 3, and 4, respectively, whereas the success rate in group 2 was 97, 93, 81, and 66% in years 1, 2, 3, and 4, respectively. CONCLUSION: Both procedures, i.e., combined trabeculotomy-trabeculectomy and Ahmed valve implantation are suitable options in advanced PCG with failed trabeculotomy and goniotomy. Ahmed valve implanation has a better long-term survival, but trabeculotomy-trabeculectomy provides a second chance for surgical intervention.

Risk of open angle glaucoma due to tumor necrosis factor alpha gene polymorphisms.

INTRODUCTION: Axonal degeneration and retinal ganglion cell apoptosis in glaucoma is associated with tumor necrosis factor alpha (TNF-α), which is an important pro-inflammatory cytokine. The aim of this study was to determine the association between the risk of open angle glaucoma (OAG) in the Egyptian population and tumor necrosis factor alpha (TNF-α) gene polymorphisms. METHODS: Sixty OAG patients and 26 healthy unrelated controls were used to analyze TNF-α polymorphism G-308A using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: the GG genotype was found at a higher frequency in the controls than in the patients, and the AA and GA genotypes were associated strongly with OAG. CONCLUSION: In this study, we found that the TNF-α polymorphism G-308A was associated significantly with OAG in the Egyptian population. However, there is a need for population-based studies with large numbers of subjects. Also, long-term follow up is required to verify the association between TNF-α polymorphism G-308A and glaucoma susceptibility.