Effect of Risk Alleles in CFH, C3, and VEGFA on the Response to Intravitreal Bevacizumab in Tunisian Patients with Neovascular Age-related Macular Degeneration.

Purpose. The aim of this pharmacogenetic study was to evaluate the impact of high-risk alleles in factor H, factor C3 and vascular endothelial growth factor (VEGF) on the response to intravitreal bevacizumab in patients with neovascular age-related macular degeneration (AMD) in a Tunisian population. Methods. Ninety patients with active neovascular AMD treated with intravitreal bevacizumab injections were enrolled in the study. Treatment response was evaluated by comparing BCVA at baseline and at 12 months. Patients were classified into either "poor responders" (PR) or "good responders" (GR). Single nucleotide polymorphism (SNP) genotyping was performed for rs1061170 in FH, rs2230199 in C3 andrs699947, rs2010963 and rs3025039 in VEGF. The association between genotype and visual response at 12 months was assessed. Results. Seventy-seven participants were assigned to the GR group and 13 to the PR group. No correlation was found between FH, C3 and VEGF variant alleles and treatment response. However, haplotype analysis of rs699947 ((- 2578) C/A), rs2010963 ((+ 405) C/G) and rs3025039 ((+ 936) C/T) SNPs revealed that the AGT haplotype was associated with a poor response at 12months (p = 0.048). No association was found between treatment response and the cumulative effect of all high-risk alleles of C3, FH and VEGF. All three types of CNV were found in both groups at a comparable frequency. Conclusions. The VEGF haplotype TGA could be used as a marker for poor visual prognosis in Tunisian patients with neovascular AMD treated with bevacizumab.

Y402H polymorphism in complement factor H and age-related macular degeneration in the Tunisian population.

To evaluate a possible association between the complement factor H (CFH) Y402H polymorphism and susceptibility to age-related macular degeneration (AMD) in the Tunisian population, as well as the impact of the genotype distribution among different phenotypes and the response to treatment with intravitreal bevacizumab, exon 9 of CFH was analyzed for the Y402H polymorphism by direct sequencing in 135 healthy controls and 127 sporadic unrelated AMD patients classified into the following groups: 12 atrophic AMD (group G1), 115 exudative AMD (G2) and 10 AMD patients who had fibrovascular scarring (G3) that did not allow a precise grading of the phenotype. Seventy patients in G2 were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization (CNV) was no longer active. The frequency of the CFH 402H allele was significantly higher in AMD patients than in controls (p = 2.62 × 10(-16)). However, subgroup analysis does not reveal any association between the variant allele H and phenotypes of AMD or CNV. Also, there was no significant difference in response to bevacizumab treatment according to Y402H CFH genotype (p = 0.59). A strong association of the 402H allele with susceptibility to AMD in the Tunisian population was confirmed; however, this variant does not appear to be involved in the clinical progression of this disease or in the postintravitreal bevacizumab response.

[Prevalence and risk factors of age-related macular degeneration (AMD) in a Tunisian hospital population]. / Prévalence et facteurs de risque de la dégénérescence maculaire liée à l'âge (DMLA) dans une population hospitalière tunisienne.

PURPOSE: To describe the prevalence and the risk factors for the age related macular degeneration (AMD) in a Tunisian hospital population. PATIENTS AND METHODS: A total of 2204 subjects 50 years of age and older were enrolled in a prospective study conducted between august 2004 and February 2009. Medical history was reviewed. Subjects underwent a complete ophthalmic examination, including best corrected visual acuity and slit lamp biomicroscopy with fundus examination. Fundus photography and fluorescein angiography were performed if clinical features of AMD were observed on fundus examination. Cases were classified in early and late stages of AMD. RESULTS: The prevalence of late AMD was higher than early AMD. Significant risk factors are age, male gender, smoking, excessive sunlight exposure and poor consumption of fish. Cardiovascular disease, diabetes and dyslipimia were not significantly associated to a high prevalence of AMD. CONCLUSION: AMD is a multifactorial disease. In our Tunisian hospital population, the prevalence of AMD was higher than in the Europeen population. It can be explained by genetic differences or risk factors. Age, cigarette smoking and sunlight exposure were associated with increasing prevalence of AMD in Tunisia.

[Characteristics of retinal detachment following neodymium YAG laser posterior capsulotomy: clinical and therapeutic aspects]. / Les décollements de rétine rhegmatogènes post-capsulotomie postérieure au laser YAG: aspects cliniques et thérapeutiques.

PURPOSE: To study the clinical characteristics and the therapeutic results of retinal detachment following neodymium YAG laser posterior capsulotomy. MATERIAL AND METHODS: A retrospective study of 28 patients (28 eyes) operated in department B of the Hédi Rais Institute of Ophthalmology (Tunis, Tunisia) between march 1993 and january 2005 for retinal detachment following neodymium YAG laser posterior capsulotomy. We study the preoperative clinical characteristics of the retinal detachment and the anatomic and functionnal results. RESULTS: The mean age of the patients is 53.4 years. Fourteen patients are men and eleven have high myopia. Ten patients are aphakic and eighteen pseudophakic. The retinal detachment is total or subtotal in 19 eyes (67.9%). The macula is detached in 27 cases (96.4%). The retinal tears are posterior in 9 cases (paravascular retinal break or macular hole) and peripheral in fifteen cases. In 4 cases no tear is found. Vitreoretinal proliferation is advanced in 10 cases. Eleven patients underwent episcleral surgery and 17 endocular surgery. The final success rate is 89%. The postoperative visual acuity increases in 20 cases. It is superior to 1/10 in 14 cases. The minimum follow-up is 6 months. CONCLUSION: The retinal detachment after neodymium laser posterior capsulotomy is serious due to severe vitreoretinal proliferation wich influences the anatomic results.

[Role of SD-OCT in the diagnosis and prognosis of macular hypoplasia in nystagmus patients]. / Apport de l'OCT-SD maculaire dans le diagnostic et le pronostic de l'hypoplasie fovéolaire chez les patients ayant un nystagmus.

PURPOSE: To investigate whether spectral domain optical coherence tomography (SD-OCT) is helpful for the diagnosis and prognosis of foveal hypoplasia in patients with overt nystagmus. METHODS: A retrospective cross-sectional study was conducted in 48 patients with overt nystagmus. All patients underwent a complete ophthalmic examination including best corrected visual acuity, biomicroscopic and fundus examinations. Spectral domain optical coherence tomography was performed using 3D OCT-2000 FA PLUS Topcon, Tokyo, Japan, for the diagnosis and grading of foveal hypoplasia, using the Thomas classification, and its possible correlation with visual acuity. RESULTS: Foveal hypoplasia was diagnosed in 6 patients (12.5%). The mean age of the patients was 13.2 years (10-18 years). Mean visual acuity was 1.53/10 (0.87 LogMAR). Foveal hypoplasia was associated with aniridia in 2 patients, albinism in 3 patients and keratoconus in 1 case. On SD-OCT, foveal hypoplasia was grade 4 in 4 patients and grade 3 in 2 patients. Mean visual acuity was 2.55/10 in patients with grade 3 foveal hypoplasia and 1.22/10 in patients with grade 4 foveal hypoplasia, and the difference in visual acuity between the two groups was statistically significant (P<0.001). CONCLUSION: SD-OCT plays a double role in the diagnosis and prognosis of foveal hypoplasia in patients with nystagmus.

[Neuro-ophthalmic adverse effects of metronidazole treatment in children: Two case studies]. / Effets secondaires neuro-ophtalmologiques du traitement par métronidazole chez l'enfant : à propos de deux cas.

PURPOSE: To report the onset of neuro-ophthalmological adverse effects in two children treated with metronidazole for amoebic dysentery. OBSERVATIONS: A 6-year-old child and his 8-year-old sister presented with sudden bilateral vision loss and diplopia associated with intense headache and vomiting. The medical history revealed amoebic dysentery 3 weeks before treated orally with metronidazole for 2 weeks. The ophthalmic examination was similar in the two children and revealed visual acuity of 3/10 bilaterally, binocular diplopia, normal oculomotor function, quiet anterior segment, altered afferent pupil light reflex associated with normal fundus examination, and most particularly absence of optic disc edema. The kinetic visual field showed restriction of isopters and blind spot enlargement and the Lancaster test showed discrete paresis of the lateral rectus muscle of the left eye. Orbitocranial computed tomography and magnetic resonance imaging were normal and visual evoked potential results were compatible with optic neuropathy. Clinical progression consisted in spontaneous resolution of general symptoms, total regression of diplopia, improvement of visual acuity, and normalization of visual evoked potentials after treatment interruption. Regression of symptomatology after interruption of the treatment allowed us to retain the toxic origin. CONCLUSION: Metronidazole may have neuro-ophthalmological side effects. These complications are rare but can be severe and are reversible after treatment interruption. Regular follow-up is necessary in children receiving this treatment.

[Intravitreal bevacizumab in AMD complicated by submacular hemorrhage]. / Injections intravitréennes de bevacizumab dans les hémorragies sous maculaires compliquant la DMLA.

PURPOSE: To evaluate functional and anatomic results of intravitreal bevacizumab as monotherapy at 12 and 24 months in patients with neovascular age-related macular degeneration (AMD) complicated by large submacular hemorrhage. METHODS: Retrospective analysis of a total of 21 patients (22 eyes) with large submacular hemorrhage secondary to age-related macular degeneration between May 2008 and December 2011. Patients were treated with three monthly intravitreal bevacizumab injections (1.25mg/0.05 mL) at a four to six week interval and then PRN. Retreatment was based on the presence of hemorrhage on fundus examination or signs of activity on optical coherence tomography. Changes from baseline best corrected visual acuity (BCVA) scores, central retinal thickness, volume of hemorrhage and number of injections were analyzed. RESULTS: The mean patient age was 72 years (range, 60-89 years). All patients completed at least 12 months of follow-up, and 17 patients fulfilled 24 months. The size of hemorrhage varied from 3 to 9 disc areas with a mean duration of 12.8 days. At baseline, mean initial BCVA was 20/400 (1.3 LogMAR) and improved to 20/160 at 12 months (P<0.001) and 20/164 at 24 months (P<0.001). Mean central retinal thickness decreased significantly from 550 µm to 255 µm at 24 months (P<0.001). The mean number of injections was 3.87 during the first 12 months. No case of recurrent bleeding was detected during the second year. CONCLUSION: Intravitreal bevacizumab may be a beneficial approach for the management of large submacular hemorrhage secondary to AMD.

[SD-OCT contribution in congenital achromatopsia diagnosis (6 patients)]. / Contribution du SD-OCT de la macula dans le diagnostic de l'achromatopsie congénitale : à propos de 6 patients.

PURPOSE: Achromatopsia (ACH) is a congenital autosomal recessive cone disorder. The puspose is to describe particular SD-OCT macular images in ACH. METHODS: The study included 6 patients from 3 consanguineous Tunisian families with congenital nystagmus and amblyopia with ACH. All patients had clinical examination with fundus photography, autofluorescence, 100-Hue Color vision and the appearance and thickness of all retinal layers were evaluated by spectral-domain optical coherence tomography (SD-OCT). RESULTS: All patients had ACH. The feature was loss of inner- and outer-segments (IS/OS) with disruption of the ciliary layer on OCT and an appearance of partial-thickness hole in the outer macular retina. CONCLUSION: This feature seems to be characteristic of ACH. SD-OCT correlated to clinic signs help the diagnosis.

[Intravitreal bevacizumab injections versus verteporferin photodynamic therapy for macular choroidal neovascularization in high myopia: 24-month follow-up]. / Traitement des néovaisseaux choroïdiens maculaires du myope fort : injection intravitréenne de bevacizumab versus photothérapie dynamique à la vertéporfine à 24 mois.

PURPOSE: To compare the long-term safety and of intravitreal bevacizumab injections (IVB) and verteporferin photodynamic therapy (PDT) in the treatment of choroidal neovascularization (CNV) in high myopia. METHODS: Review of retrospectively collected data of 60 eyes of 60 patients with high myopic choroidal neovascularization treated either with standard PDT (PDT group; n=30) or IVB injections (IVB group; n=30). The two groups were compared at baseline, 3, 6,12 and 24 months. RESULTS: In the IVB group, mean best corrected visual acuity (BCVA) was significantly improved at 3 to 12 months; however, the significance was lost at 24 months. The PDT group showed an insignificant improvement at 3 and 6 months, then worsened at 12 and 24 months. Mean BCVA was better in the IVB group than the PDT group at 3, 6, 12 and 24 months. The decrease in mean central macular thickness was significantly higher in the IVB group than in the PDT group at 3, 6, 12 and 24 months. At 24 months, chorioretinal atrophy was noted in five eyes (16.6%) treated with IVB and in 22 eyes (73.3%) treated with PDT (P=2×10(-5)). CONCLUSION: IVB provides significantly better BCVA than PDT for high myopic CNV over the long-term.

[Internal astigmatism with other ocular lesions]. / Astigmatisme interne et lésions oculaires associées.

Astigmatism is a refractive defect whose origin is not always purely corneal, and is sometimes the result of corneal, crystalline lens or mixte contributions. The aim of our study is to report, through two cases, ocular lesions associated with a lenticular astigmatism and their evolution after treatment. In the first observation, it is a 25-year-old patient with a unilateral extra corneal astigmatism within the framework of the "tilted disc syndrome" associated with bilateral myopia. This patient has received treatment by Lasik. The postoperative course was good with a decline of 5 ans. The second observation is that of a patient aged 35 years without having a general history with a posterior lenticonus associated with keratoconus responsible for a major mixed astigmatism. She received combined surgery: penetrating keratoplasty with lens extraction and implantation of an artificial lens. The evolution was good with good visual recovery. The balance of internal astigmatism must include the systematic achievement of a subjective and objective refraction under cycloplegia and corneal topography. The search for etiology is critical to screen for eye or general disease and guide the therapeutic strategy. Knowledge of the refractive power of the cornea and crystalline lens of astigmatism separately would be important for surgery refractive and crystalline lens surgery.

[Vogt-Koyanagi-Harada disease associated with interferon-alpha and ribavirin therapy for chronic hepatitis C infection]. / Syndrome de Vogt-Koyanagi-Harada au cours d'une hépatite C chronique sous interféron alpha et ribavirine.

The complex immunological effects of interferon and ribavirin therapy in hepatitis C virus may also exacerbate or trigger the development of autoimmunity. A rare case of Vogt-Koyanagi-Harada disease associated with ribavirin and interferon-alpha treatment for chronic hepatitis C infection is presented. The potential role of interferon and/or ribavirin therapy is discussed. Physicians should be aware of the association between interferon-alpha 2a and ribavirin use for hepatitis C infection and the development of Harada disease. This severe ophthalmological complication requires close follow-up of hepatitis C virus-infected patients on interferon-alpha treatment.

[Late recurrent retinal detachment after scleral buckling]. / Récidives tardives des décollements de rétine après chirurgie épisclérale.

PURPOSE: To analyze the physiopathologic mechanism, therapeutic modalities, and prognosis of late recurrent retinal detachment. METHODS: A retrospective study was conducted on late recurrent retinal detachment operated with episcleral surgery over a 15-year period. Ten patients were included in this study. RESULTS: Late recurrent retinal detachments occurred in 0.39% of all retinal detachments repaired by episcleral surgery over 15 years. Redetachment occurred 3-7 years after surgery, with etiologies including new retinal breaks (seven cases), reopening of old breaks (three cases), and removal of scleral explant (one case). Proliferative vitreoretinopathy (PVR) grade B was seen in three cases, grade C in six cases, and grade D in one case. After reoperation, the retina was reattached in nine cases. Three eyes were treated with scleral buckle, the others underwent vitreoretinal surgery. Failure occurred in one patient who had a very high level of vitreoretinal proliferation. CONCLUSION: Late recurrent retinal detachments are rare and vitreous base traction seems to be an important factor, although the associated PVR was probably a secondary factor. Treatment depends on PVR, with vitreoretinal surgery necessary in some cases. They usually have a good prognosis.