Genotype-phenotype associations in CRB1 bi-allelic patients: a novel mutation, a systematic review and meta-analysis.

PURPOSE: The goal of the study was to search for novel bi-allelic CRB1 mutations, and then to analyze the CRB1 literature at the genotypic and phenotypic levels. APPROACH: We screened various variables such as the CRB1 mutation types, domains, exons, and genotypes and their relation with specific ocular phenotypes. An emphasis was given to the bi-allelic missense and nonsense mutations because of their high prevalence compared to other mutation types. Finally, we quantified the effect of various non-modifiable factors over the best-corrected visual acuity oculus uterque (BCVA OU) using multivariate linear regression models and identified genetic interactions. RESULTS: A novel bi-allelic missense in the exon 9 of CRB1; c.2936G > A; p.(Gly979Asp) was found to be associated with rod-cone dystrophy (RCD). CRB1 mutation type, exons, domains, and genotype distribution varied significantly according to fundus characteristics, such as peripheral pigmentation and condition, optic disc, vessels, macular condition, and pigmentation (P < 0.05). Of the 154 articles retrieved from PubMed, 96 studies with 439 bi-allelic CRB1 patients were included. Missense mutations were significantly associated with an absence of macular pigments, pale optic disc, and periphery pigmentation, resulting in a higher risk of RCD (P < 0.05). In contrast, homozygous nonsense mutations were associated with macular pigments, periphery pigments, and a high risk of LCA (P < 0.05) and increased BCVA OU levels. We found that age, mutation types, and inherited retinal diseases were critical determinants of BCVA OU as they significantly increased it by 33% 26%, and 38%, respectively (P < 0.05). Loss of function alleles additively increased the risk of LCA, with nonsense having a more profound effect than indels. Finally, our analysis showed that p.(Cys948Tyr) and p.(Lys801Ter) and p.(Lys801Ter); p.(Cys896Ter) might interact to modify BCVA OU levels. CONCLUSION: This meta-analysis updated the literature and identified genotype-phenotype associations in bi-allelic CRB1 patients.

Safety, Efficacy, and Predictive Factors of Conventional Epithelium-Off Corneal Crosslinking in the Treatment of Progressive Keratoconus.

PURPOSE: To report predictive factors of outcome of conventional epithelium-off corneal crosslinking (CXL) in the treatment of progressive keratoconus. METHODS: This is a monocentric observational retrospective study conducted at Eye and Ear International Hospital, Lebanon. All patients with progressive keratoconus who underwent CXL between January 2008 and January 2016, with minimal 3-years follow-up were included. Primary treatment outcomes were maximum keratometry (K max), best-corrected distance visual acuity (CDVA), and failure. Failure was defined as an increase of 1.00 diopters (D) or more in K max and/or an increase of 0.1 logMAR or more in CDVA and conversion to corneal transplantation. Statistical analysis was done to identify predictors of treatment success. Univariate and multivariate analyses were performed to determine the correlations between baseline parameters and outcomes, and an equation for predicting K max and CDVA was created. RESULTS: 156 eyes of 102 patients were enrolled. The mean age was 23.85 ± 6.52 years. Failure occurred in 31 eyes (19.87%). Gender and thinnest pachymetry did not have any impact on postoperative outcomes. Concerning the CDVA outcome, multivariate analysis showed that a better preoperative CDVA was associated with higher improvement in CDVA, and higher baseline K max and higher posterior mean K were associated with a worse outcome CDVA. Regarding postoperative K max, a higher baseline K max, a worse baseline CDVA, and a younger age were associated with less flattening postoperatively. CONCLUSION: CXL is a safe and effective method in treating progressive keratoconus. However, the clinical benefits can differ among patients, and in our series, a nonnegligible number of cases show a continued progression of their ectasia. Further studies to identify predictors of postoperative progression prior to the procedure could help sort out good responders to treatment.

Comparison of Efficacy and Ocular Surface Disease Index Score between Bimatoprost, Latanoprost, Travoprost, and Tafluprost in Glaucoma Patients.

AIM: The purpose of this study is to evaluate and compare the efficacy of 4 prostaglandin analogues (PGAs) and to determine the incidence of ocular surface disease in newly diagnosed, primary open-angle glaucoma (POAG) patients started on one of those 4 PGAs: bimatoprost (benzalkonium chloride, BAK, 0.3 mg/mL), latanoprost (BAK 0.2 mg/mL), travoprost (polyquad), and tafluprost (BAK-free). PATIENTS AND METHODS: In this single-center, open-label trial, 32 patients newly diagnosed with POAG were randomly started on one of the four PGAs. All patients underwent a complete ophthalmological exam at presentation and at 1, 3, and 6 months of follow-up. Dry eye disease (DED) was assessed using the original Ocular Surface Disease Index (OSDI) questionnaire, in order to evaluate the impact of the drops on the quality of life of patients. RESULTS: The mean age was 60.06 years ± 11.76. All four drugs equally and significantly reduced the intraocular pressure (IOP) with respect to the baseline IOP. There was a trend for a slightly greater reduction of IOP with bimatoprost, but the difference was not found to be statistically significant when compared to other PGAs. OSDI scores were significantly superior for travoprost (10.68 ± 5.73) compared to the other three drugs (p < 0.05). Latanoprost caused the most significant eyelash growth and iris discoloration. Conjunctival hyperemia and superficial keratitis occurrence were similar in the four groups. CONCLUSION: All prostaglandin analogues equally and significantly reduce the IOP in patients with POAG. According to the results of the OSDI score, latanoprost seems to be the least tolerated among the four drugs.

EFFICACY OF INTRAVITREAL RANIBIZUMAB INJECTIONS IN THE TREATMENT OF VITREOUS HEMORRHAGE RELATED TO PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To investigate the efficacy of intravitreal ranibizumab injections in proliferative diabetic retinopathy associated with vitreous hemorrhage (VH). METHODS: A prospective study including patients with proliferative diabetic retinopathy who presented with persistent VH. Vitreous hemorrhage was graded into mild, moderate, and severe. Patients were randomized into two groups: the ranibizumab group was treated with intravitreal injections of ranibizumab and the control group was assigned to observation alone. Vitrectomy was performed if there was any aggravation of the VH in patients with mild, moderate, and severe VH or in the absence of improvement by 16 weeks in patients with moderate and severe VH. RESULTS: The ranibizumab group included 71 patients and the control group included 62 patients. There was a statistically significant difference in the vitrectomy rate in patients with mild-to-moderate VH (5 patients [7.04%] and 12 patients [19.35%], respectively; P = 0.04). However, there was no statistically significant difference in the overall vitrectomy rate, and in the vitrectomy rate in severe VH (17 [23.94%] and 12 [16.90%] patients in the ranibizumab group vs. 22 [35.48%] and 10 [16.13%] patients in the control group, P = 0.14 and P = 0.83, respectively). Recurrence of the VH occurred in 22 patients in the ranibizumab group and 29 patients in the control group (P = 0.06). Better visual acuity measurements were recorded on all follow-up visits in the ranibizumab group (P ≤ 0.04). CONCLUSION: Intravitreal ranibizumab injections could be considered in proliferative diabetic retinopathy patients with mild and moderate VH.

Survival Pattern of Hodgkin Lymphoma Patients in the Last 25 Years in Lebanon.

CONTEXT: After the emergence of combination chemotherapy in 1960s, survival of patients with Hodgkin lymphoma (HL) has dramatically improved worldwide. We lack studies that document the favorable evolution of survival regarding this disease in Lebanon. OBJECTIVE: To compare the overall survival in HL over 3 different decades in Lebanon. METHODS: We retrospectively reviewed the charts of 196 patients diagnosed with HL, treated and followed from 1990 to 2015 in our center. Patients were divided into 3 groups according to period of analysis: group A (1990-1999), group B (2000-2009), and group C (2010-2015). We studied the characteristics and survival patterns of patients in each group. RESULTS: The male-to-female sex ratio was 1.06. The median age at diagnosis was 33 years in group A, 30.4 in group B, and 33.12 in group C (P = .6). Results showed variations in the subtypes of the disease according to the following: nodular-sclerosis HL 59.5% in group A, 76.2% in group B, and 85.4% in group C. Mixed cellularity HL 21.6% in group A, 2.4% in group B, and 73.7% in group C (P = .0001). Patients presented with localized disease in 58.6%, 73.7%, and 56.4% in groups A, B, and C, respectively (P = .173). Complete remission was achieved in 76.5% in group A, 85.3% in group B, and 69.5% in group C (P = .007). The survival rate at 5 years in group A was 91%, 94% in group B, and 100% in group C. CONCLUSION: The survival of patients with HL has dramatically improved over the past 25 years in Lebanon. These results resemble those achieved in Western countries due to the fast adoption of new molecular imaging technologies at diagnosis and follow-up and the rapid approval of new drugs for relapse in the Lebanese market.

Long-term results of Ahmed glaucoma valve in association with intravitreal bevacizumab in neovascular glaucoma.

PURPOSE: Evaluate the long-term results of the Ahmed glaucoma valve (AGV) surgery in association with bevacizumab (Avastin) in neovascular glaucoma (NVG) patients. DESIGN AND METHODS: This retrospective institutional study reviewed 39 eyes of 34 patients with NVG who underwent AGV implantation. The intravitreal bevacizumab (IVB) group included 19 eyes that received an injection of IVB 7 days preoperatively, whereas the no-IVB group included 20 eyes that did not receive any antivascular endothelial growth factor therapy. Findings such as intraocular pressure (IOP), number of antiglaucoma medications, best-corrected visual acuity (BCVA), and surgical outcomes were reviewed over a period of 5 years. RESULTS: There were no significant differences in the preoperative characteristics between the 2 groups. At last follow-up visit, IOP was 16.37±5.72 mm Hg in the IVB group and 20.05±9.75 mm Hg in the no-IVB group (P=0.16). The number of postoperative antiglaucoma medications was significantly lower in the IVB group (P=0.02). Last visit's mean BCVA was 2.34±1.00 logMAR in the IVB group and 2.66±1.04 logMAR in the control group (P=0.33). Hyphema was significantly less observed in the IVB group (P=0.02). The probability of success was 63.2% in the IVB group and 70.0% in the control group (P=0.37). CONCLUSIONS: Preoperative IVB before AGV was not associated with a better surgical success, IOP control, or BCVA. Its administration significantly decreased postoperative hyphema and number of last visit's antiglaucoma medications.