Razek Georges Coussa

Choroideremia: A review of general findings and pathogenesis

Choroideremia (CHM) is an X-linked retinal dystrophy belonging to the family of blinding disorders. It is characterized by progressive degeneration of the choriocapillaris, retinal pigment epithelium and photoreceptors. CHM is caused by mutations in the Rab Escort Protein 1 (REP-1) gene, which encodes a protein involved in vesicular trafficking. This paper gives an overview of the clinical features, visual function, biochemistry, histology, molecular genetics, pathogenesis, diagnosis and treatment of CHM.

Choroideremia: Effect of age on visual acuity in patients and female carriers

Background/aims: The extent and time course of vision loss in Choroideremia (CHM) is still unclear. We undertook this study to quantitate the change in visual acuity (VA) over time in order to gain a better understanding of the natural course of this retinal disorder. Methods: Corrected VA of 120 males with CHM and 53 female carriers were collected from 24 studies and/or case reports published between 1981 and 2010, as well as from data on 15 patients examined at the Cole Eye Institute (Cleveland Clinic). Cross-sectional and longitudinal analyses were used to investigate the relationship between VA and age, as well as the progression rate of VA with age, respectively. Age grouping effects were investigated using ANOVA. Results: The mean age of affected males was 36.6 ± 17.7 years. The mean logMAR VA was 0.35 ± 0.53. There was a significant 0.0072 decrease in logMAR VA per year (p = 1.22 × 10-4). There was a significant difference between VA of patients <50 years of age and those >50 years (0.27 ± 0.39 vs. 0.61 ± 0.81, p = 2.90 × 10-5). When we compared the rate of VA loss for patients <50 years vs. those >50 years, we also found a significant difference (0.01 ± 0.04 vs. 0.06 ± 0.08, p = 1.23 × 10-2). The average age of female carriers was 36.4 ± 17.7 years, with an average logMAR VA of 0.36 ± 0.6. There was no significant correlation between VA of female carriers and age (p = 0.12) with 46% of female carriers having a VA better than 20/20 at an average age of 33 years compared to 25% of affected males at 30 years. Conclusion: In affected males with CHM, VA decreases very slowly until subjects reach 50 years of age, at which time the rate and extent of vision loss become significantly higher. Additionally, VA decreases more rapidly as individuals get older. In contradistinction to affected males, VA loss in female carriers is much milder.

Predictors of visual acuity and genotype-phenotype correlates in a cohort of patients with Stargardt disease

Purpose To assess the genotypic diversity in patients with Stargardt disease and to characterise epidemiological and genotypic predictors of phenotype. Methods Retrospective, cross-sectional study of 112 patients with Stargardt disease. We evaluated the correlation between age at presentation, best-corrected visual acuity (BCVA), and ABCA4 genotypes. Results Mean age at presentation was 30±16 years (range 6–78 years) for the 112 patients of 104 families. 98 of 90 families had a probable molecular diagnosis. We found that BCVA is not related to age of presentation in a linear or polynomial manner; that BCVA of patients presenting in the first decade was significantly worse than those presenting in later decades (p=0.04); that patients who harboured two or more mutations presented earlier and had worse BCVA than those with no or 1 mutation identified by any method of testing (n=112, p=3.29×10−6) or by full sequencing (n=32, p=0.02); that 16 patients with c.5882G>A allele demonstrated better BCVA than the remaining patients (p=0.01); and that 10 patients with the c.5461-10T>C mutation presented earlier (p=0.02×10−5) and had more severe disease. Conclusions Epidemiological and genotypical findings portend visual prognosis in patients with Stargardt disease. Select sequence variations in ABCA4 may confer a specific phenotype. The present data will help in assessing patients for emerging therapies.

Surgical management of lens subluxation in Marfan syndrome

PURPOSE To review the literature on the surgical management, describe a simplified surgical technique, and to report the postoperative clinical course of ectopia lentis removal in patients with Marfan syndrome. METHODS The medical records of patients with a clinical diagnosis of Marfan syndrome and clinically significant lens subluxation were retrospectively reviewed. Patients underwent lens extraction by a single surgeon via a simplified anterior segment approach. The pre- and postoperative best-corrected visual acuity, biometric measurements, intraocular pressure, and incidence of surgery-related complications were reviewed. RESULTS A total of 42 eyes of 22 patients were included. Mean postoperative follow-up was 4.9 ± 2.9 years (range, 1-10 years). Average age at surgery was 10.2 ± 9.2 years (range, 2-37 years), with 18 patients (36 eyes) ≤ 18 years of age. The average preoperative best-corrected visual acuity was 20/80, and the average postoperative best-corrected visual acuity at last follow-up was 20/25, with an average improvement of 6 lines on the Snellen chart. All eyes had a best-corrected visual acuity > 20/30 at last follow-up with aphakic correction. One eye of 1 patient developed a retinal detachment following blunt trauma. No other intra- or postoperative complications were reported. CONCLUSIONS Anterior lensectomy and limited vitrectomy with aphakic correction is safe and provides a consistent visual outcome in patients with lens subluxation secondary to Marfan syndrome. This is especially important in pediatric patients, in whom long-term follow-up for iris- and scleral-fixated intraocular lenses is limited.

Post-transplant venous thromboembolic events and their effect on graft survival.

Venous thromboembolic events (VTEs) are a major cause of post-operative morbidity and mortality. Our objective is to establish the prevalence of VTEs in kidney transplant recipients and assess its impact on graft survival. Data regarding renal transplant patients with VTEs from 1985 to 2010 were identified and analyzed. After excluding recipients of combined grafts and late VTE development, 1596 recipients were included in this analysis. The prevalence of post-operative VTEs and graft survival were determined. Cox regression was used to analyze the survival data and data on prognostic (confounding) variables. The observed prevalence of VTEs in kidney transplant recipients was 1.6%. Of the 1596 kidney recipients, 25 recipients who developed VTEs had a mean graft survival of 12.3 years (compared with 20.5 years in patients without). The hazard ratio was 1.1 (95% confidence interval: 0.4-3.0, P = 0.447). The prevalence of VTEs post kidney transplantation is small. Although it did not reach statistical significance, it increased the risk of graft failure by 30%.

Oral Microencapsulated Live Saccharomyces cerevisiae Cells for Use in Renal Failure Uremia: Preparation and In Vivo Analysis

Orally administrable alginate-poly-L-lysine-alginate (APA) microcapsules containing live yeast cells was investigated for use in renal failure. At all times, yeast cells remain inside the microcapsules, which are then excreted in the stool. During their gastrointestinal passage, small molecules, like urea, diffuse into the yeast microcapsules where they are hydrolyzed. Orally administrating these microcapsules to uremic rats was found to decrease urea concentrations from 7.29 ± 0.89 mmol/L to 6.12 ± 0.90 mmol/L over a treatment period of eight weeks. After stopping the treatment, the urea concentrations increased back to uremic levels of 7.64 ± 0.77 mmol/L. The analysis of creatinine concentrations averaged 39.19 ± 4.33 μmol/L, 50.83 ± 5.55 μmol/L, and 50.28 ± 7.10 μmol/L for the normal-control, uremic-control and uremic-treatment groups, respectively. While creatinine concentrations for both uremic-control and uremic-treatment groups did not differ among each other (P > .05), they were, however, significantly higher than those of the normal control group (P < .05). Uric acid concentrations averaged 80.08 ± 26.49 μmol/L, 99.92 ± 26.55 μmol/L, and 86.49 ± 28.42 μmol/L for the normal-control, uremic-control and uremic-treatment groups, respectively. There were no significant differences in both calcium and phosphate concentrations among all three groups (P > .05). The microbial populations of five tested types of bacteria were not substantially altered by the presence of the yeast APA encapsulated yeast (P > .05).

Potentials and limitations of microorganisms as renal failure biotherapeutics

Renal insufficiency leads to uremia, a complicated syndrome. It thus becomes vital to reduce waste metabolites and regulate water and electrolytes in kidney failure. The most common treatment of this disease is either dialysis or transplantation. Although these treatments are very effective, they are extremely costly. Recently artificial cells, microencapsulated live bacterial cells, and other cells have been studied to manage renal failure metabolic wastes. The procedure for microencapsulation of biologically active material is well documented and offers many biomedical applications. Microencapsulated bacteria have been documented to efficiently remove urea and several uremic markers such as ammonia, creatinine, uric acid, phosphate, potassium, magnesium, sodium, and chloride. These bacteria also have further potential as biotherapeutic agents because they can be engineered to remove selected unwanted waste. This application has enormous potential for removal of waste metabolites and electrolytes in renal failure as well as other diseases such as liver failure, phenylketonuria, and Crohn’s disease, to name a few. This paper discusses the various options available to date to manage renal failure metabolites and focuses on the potential of using encapsulated live cells as biotherapeutic agents to control renal failure waste metabolites and electrolytes.

Primary Combined Pars Plana Vitrectomy and Phacoemulsification With Anterior Segment Removal of Posterior Segment Intraocular Foreign Bodies: A 30-Month Longitudinal Study:

Purpose: To describe a surgical technique and report visual and anatomical outcomes after primary combined pars plana vitrectomy (PPV) and phacoemulsification in patients with posterior segment intraocular foreign bodies (IOFBs) removed via the anterior chamber without enlarging preexisting sclerotomies. Posterior IOFBs are generally managed in a stepwise surgery consisting of phacoemulsification/lensectomy for traumatic cataract removal then PPV and removal of IOFB through enlarged sclerotomies. Enlarged sclerotomies may carry a significant risk of hypotony, vitreous hemorrhage, vitreous and retinal incarceration, and rhegmatogenous retinal detachment with proliferative vitreoretinopathy. Limited studies exist on long-term results of primary anterior segment removal of posterior IOFB combined with primary phacoemulsification. Methods: Medical records of consecutive patients who had ocular lacerations and posterior segment IOFB between October 2003 and June 2017 in a university hospital were reviewed. Patients who received a combined primary IOFB removal and phacoemulsification were included in the study. The postoperative evolution including visual acuity and complications were all recorded. Results: Thirteen patients (13 eyes) were included in the study. All patients were men, and the average age at presentation was 38 years. All IOFB were metallic, and their size ranged from 2 to 7 mm. All patients were operated within 24 hours of presentation. Six (46%) of the 13 lacerations were corneal, and 7 (54%) were scleral. Overall, 9 of 13 (69%) had a final postoperative best-corrected visual acuity equal to or better than 20 of 25. There were 3 (23%) postoperative complications of recurrent rhegmatogenous retinal detachment that occurred within the first postoperative year. Conclusion: Primary combined PPV and phacoemulsification with the removal of IOFB via the anterior segment is a safe and promising approach for repairing open globe injuries. Our results demonstrate the favorable prognostic benefit of this technique, which is recommended in cases with small corneal laceration and posterior segment pathology resulting from IOFB.

Data for: Retrobulbar Anaesthesia for Adjustable Strabismus Surgery in Adults: A Prospective Observational Study

OBJECTIVE To characterize the ocular response to retrobulbar anaesthesia and to evaluate the efficacy of retrobulbar anaesthesia for adjustable strabismus surgery in adults. DESIGN Prospective observational study. PARTICIPANTS Adult patients undergoing adjustable strabismus surgery under retrobulbar anaesthesia. METHODS Surgical success was defined by ocular alignment within 10 prism diopters (PD) of orthotropia for horizontal rectus surgery and within 5 PD for vertical rectus surgery. After retrobulbar injection of Xylocaine with epinephrine, the onset time and the degree of visual impairment, ocular akinesia, and analgesia were evaluated. Postoperative parameters included the restoration of vision, onset of pain, resolution of ptosis, normalization of pupil, resolution of extraocular motility deficits, and the timing of postoperative adjustment. Perioperative complications were also documented. RESULTS A total of 33 patients were initially included in this study. Two patients experienced complications (perioperative retrobulbar hemorrhage, postoperative suprachoroidal hemorrhage) and were excluded from data analysis. Of the remaining 31 patients (mean age, 50.2 ± 14.8 years), surgical outcome was satisfactory in 30/31 (96.8%) patients at the first postoperative visit and in 15/19 (78.9%) cases at last follow-up (mean, 6.1 ± 1.6 months). Excellent intraoperative ocular akinesia and analgesia was achieved with retrobulbar anaesthesia. After retrobulbar injection, visual impairment was the first to resolve to preoperative levels within (mean ± SD) 3.7 ± 1.9 hours postinjection, followed by onset of pain at 4.1 ± 1.0 hours, resolution of ptosis at 4.3 ± 1.9 hours, and normalization of pupil reactivity at 6.1 ± 1.0 hours. The resolution of anaesthesia upon extraocular motility occurred within 5.7 ± 1.0 hours postinjection (range, 4.5-8.0 hours), allowing for subsequent same-day postoperative adjustment. CONCLUSIONS Retrobulbar anaesthesia in the context of adult, adjustable strabismus surgery is a relatively safe and effective technique. It provides excellent intraoperative analgesia and akinesia. Retrobulbar anaesthesia enables for same-day suture adjustments to be reliably performed.

HLA-A29 negative Birdshot-like chorioretinopathy associated with common variable immunodeficiency

Purpose To report the longest ophthalmic follow-up and the associated ocular complications of HLA-A29 negative Birdshot-like chorioretinopathy (BLCR) associated with common variable immunodeficiency (CVID). Observations A 22-year-old man known for CVID presented with a 3-month history of decreased visual acuity OS. Funduscopy revealed significant cystoid macular edema OS, as well as optic disk edema and chorioretinal infiltrates without signs of vitritis OU. No infectious, inflammatory or neoplastic etiologies were identified. He subsequently received one dose of intravitreal triamcinolone OS which completely resolved the macular edema. The optic nerve edema persisted despite the addition of intravenous immunoglobulin. His visual acuity was 20/20 OU at the 24th follow-up month. Conclusion and importance: To our knowledge, this is the third case of HLA-A29 negative BLCR associated with CVID. It is the first case with long-term follow-up providing, in consequence, the best understanding of the natural history and possible complications of this rare disease. Aggressive systemic treatment, in collaboration with an immunologist, is generally needed to control the ophthalmic complications.