Retinal changes in multiple sclerosis: An optical coherence tomography and angiography study.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system with neuroaxonal damage. It is the principal driver of non-traumatic disability in young adults. Visual symptoms are common and optic neuritis (ON) may be the revealing feature in up to 30% of cases. Structural optical coherence tomography (OCT) represents a biomarker of central nervous system neurodegeneration in MS. OCT-angiography (OCT-A) is a noninvasive tool allowing the study of retinal vasculature and the detection of microvascular damage in neuro-retinal diseases. In this study, we aimed to assess structural and microvascular retinal changes in patients with MS with and without ON and to correlate the findings with visual function and MS disability. METHODS: We conducted a cross-sectional study including patients diagnosed with MS according to the 2017 McDonald criteria. All patients underwent complete neurological examination with evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS) and an ophthalmological examination including OCT and OCT-A. Patients were compared with age- and sex-matched healthy subjects. The primary endpoints were assessment of retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL+), and ganglion cell complex (GCL++) thicknesses on OCT. Vascular densities in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) were assessed on OCT-A, as well as central avascular zone (CAZ) parameters, lacunarity and fractal dimension. RESULTS: A total of 160 MS eyes with and without a previous history of ON and 64 age- and gender-matched healthy eyes were analyzed. Among 160 eyes with MS, 69 had a history of ON. We observed a decrease in RNFL and GCL++ thickness in all 12 quadrants in MS patients when compared to healthy controls. Multivariate analysis by linear regression noted a significant correlation for temporal GCL++ and inferonasal RNFL thickness that were decreased in the MS group. A greater decrease in retinal layers thickness was identified in MS patients with a history of ON. On OCT-A, vascular density in (SCP) was significantly reduced in the MS group (P<0.002). A significant correlation between RNFL thickness and retinal vascular density was found but only in less than half of the hourly quadrants. A significant correlation was noted between visual acuity and CC density (P<0.0001). We also noted an inverse correlation between EDSS scores and CC density (P=0.02 and r=-0.275) and between MSSS and RNFL/GCL++ thicknesses. CONCLUSIONS: RNFL and GCL++ layers were thinner in MS patients with a history of ON and were reversely correlated with disease severity. Moreover, retinal vascular changes were observed in MS even in eyes without ON, and CC was reversely correlated with visual function and current disability. Thus, structural OCT coupled with OCT-A could represent a noninvasive and dynamic biomarker of MS severity and progression.

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.

[Management of rhegmatogenous retinal detachment with unseen breaks: about 50 cases]. / Prise en charge des decollements de retine rhegmatogenes sans dechirure visible: a propos de 50 cas.

PURPOSE: To evaluate the clinical and therapeutic characteristics of rhegmatogenous retinal detachment (RRD) with unseen retinal breaks. PATIENTS AND METHODS: Retrospective study 50 eyes (50 patients) with RRD with unseen retinal breaks in the pre and intraoperative examination. These patients were treated between 2005 and 2010 by vitrectomy or scleral buckling. Retinal breaks were meticulously sought by indentation of the vitreous base. The subretinal fluid was drained by a peripheral retinotomy when a vitrectomy was needed and puncture ab externo when a scleral buckling was performed. RESULTS: A retinal detachment with unseen retinal breaks accounted for 15% of all RRD operated during this 5-year duration period (2005 - 2010). The average age of our patients was 57 years.Ten were myopic (20%) and 27 (54%) pseudophakic, with inferior RRD in 60% of the cases cases while advanced vitreoretinal proliferation (PVR) greater or equal to stage C in was present in 72%. Primary vitrectomy was performed in 46 cases. Retinal reattachment rate was achieved after a single procedure in 41 eyes (82%). Among them, 40 were operated by vitrectomy and one eye by scleral buckling. The recurrence rate was significantly higher in patients operated by scleral buckling (75%) than by vitrectomy (15%). CONCLUSION: RRD with unseen retinal breaks are often seen inferiorly and have a chronic evolution (60%). They concern pseudophakic patients in the majority of the cases. Their poor prognosis and high recurrence rate also appear to be related to an advanced PVR (72%). The good results of primary vitrectomy should be confirmed by randomized studies, especially in phakic eyes.

Combined central retinal artery occlusion and anterior ischemic optic neuropathy as presenting signs of systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is a chronic auto-immune condition with systemic and ocular involvement. Ophthalmological findings are diverse and can involve all layers of the globe. Posterior segment manifestations can include lupus retinopathy, retinal vascular occlusions and lupus choroidopathy. We report here a rare case of central retinal artery occlusion (CRAO) associated with anterior ischemic optic neuropathy (AION) in a young female patient as presenting signs of SLE. In this case report, we highlight a very uncommon initial presentation of this severe systemic vasculitis. A multidisciplinary approach is required in order to prevent life-threatening vaso-occlusive complications.

[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.

[Clinical characteristics and therapeutic challenges of retinal detachment in highly myopic eyes]. / Particularités cliniques et thérapeutiques du décollement de rétine du myope fort: à propos de 83 cas.

PURPOSE: To evaluate the clinical characteristics and therapeutic challenges of retinal detachment in highly myopic eyes. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 83 eyes in 79 patients with high myopia (> 6.00 diopters or axial length > or = 26.00 mm) who underwent surgery for retinal detachment between 2001 and 2008. The surgical approaches depended on the type and location of the retinal break, the degree of myopia, and the grade of PVR. RESULTS: The mean age of patients (48 men and 31 women) was 53.9 years. Refractive error ranged from - 10 D to - 25 D (mean was - 14.0 D). The mean follow-up was 19.4 months. Peripheral or equatorial retinal tears were present in 52 cases (62.6%), a macular hole in 14 cases (16.8%), a giant retinal tear in 6 cases (7.2%), and posterior paravascular retinal tears in 11 cases (13.2%). Single-surgery anatomic success was achieved in 65 cases (78.3%), with 17 cases after scleral buckle surgery and 46 cases after pars plana vitrectomy. Final anatomic success was achieved in 76 cases (91.5%). Per and postoperative hemorrhagic complications occurred in 16 cases (19.2%). CONCLUSION: Retinal detachment is a serious complication of high myopia. It often occurs in young patients. Treatment is difficult due to anatomical and clinical conditions.

Contribution of OCT angiography in angioid streaks.

PURPOSE: To study the appearance of angioid streaks (AS) in swept source optical coherence tomography angiography. METHODS: Retrospective observational study of 16 patients (31 eyes) with various stages of AS. All included patients underwent complete ophthalmologic examinations including best-corrected visual acuity (BCVA), slit-lamp examination, indirect ophthalmoscopy and fundus photography. Swept source optical coherence tomography (SS-OCT), OCT angiography (OCT-A) and fluorescein angiography were also performed. RESULTS: En face OCT detected hyper-reflective points in 65% of cases, with a choriocapillaris (CC) shadow on the corresponding OCT-A. Diffuse CC rarefaction was detected in 94%. In eyes without neovascular complications, streaks were visible as a hyposignal in the outer retina. An irregular vascular network (IVN) was detected in 80% of eyes. It filled the spaces between the AS and corresponded to flat elevation of the retinal pigmentary epithelium. Twenty-four eyes had choroidal neovascularization (CNV). CNV was type 1 in 8%, type 2 in 43%, mixed in 20% and unclassified in 29% because of a large scar. We found multiple sites of CNV in 8% of cases. CNV shape was tangled in 66% and in 2 eyes with newly diagnosed CNV. OCT-A showed a perilesional halo around new CNV. The morphology and configuration of neovascular network follow the IVN and the path of the AS and arises in proximity to sites of BM disruption. CONCLUSION: OCT-A allows early detection and monitoring of AS and their neovascular complications. It shows CC rarefaction, IVN and a predominantly tangled shape of CNV. However, there are some limitations associated with difficulty in characterizing signs of CNV activity.

[Contribution of multimodal imaging in the various stages of Stargardt disease]. / Intérêt de l'imagerie multimodale dans les différents stades de la maladie de Stargardt.

PURPOSE: To describe the contribution of multimodal imaging in the various stages of Stargardt disease (STGD). PATIENTS AND METHODS: We retrospectively reviewed 46 eyes of 23 STGD patients with identified ABCA4 mutations. All patients underwent a complete ophthalmic examination, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), fluorescein angiography (FA) and Indocyanine green angiography (ICGA). RESULTS: The mean age of patients was 25.5 years (range 8-56). Fundus examination was normal in 2 patients (subclinical stage), where SD-OCT showed localized retrofoveolar retinal pigment epithelium (RPE) thickening. FAF was normal in 1 eye and showed mild heterogeneous hyper-FAF in 3 eyes. Twelve eyes had mild salt and pepper changes in the macula (early stage) with diffuse retinal atrophy on SD-OCT and mixed hyper and hypoautofluorescence on FAF. Nine patients showed central atrophy with white-yellow flecks distributed in the posterior pole and mid-periphery. This phenotype showed total foveal atrophy on SD-OCT and normal peripapillary area on FAF. Twelve eyes had a large demarcated area of RPE atrophy, pigment clumping and migration extending to the peripheral retina associated with peripapillary atrophy. These eyes showed diffuse retinochoroidal atrophy on OCT with diffuse alterations reaching the peripapillary area on FAF. On FA, it was difficult to analyze the choroidal silence sign in patients with advanced stages of the disease. A hyperfluorescent window defect pattern was also found in patients with white-yellow flecks and did not correspond exactly to them, or to the areas of peripheral autofluorescent lesions. ICGA showed hypocyanescent areas seen at intermediate and late phases with multiple cyanescent points adjacent to them. On ICGA, hypocyanescent areas were more extensive than lesions observed on FAF. CONCLUSIONS: Multimodal imaging is helpful for the diagnosis of early stages of STGD disease and to better understand its pathophysiology. FAF and mostly SD-OCT have supplanted FA in the early, especially subclinical, stages. Over all, ICGA shows more extensive damage, making this tool useful for better understanding STGD and suggesting possible direct damage to the choriocapillaris associated with RPE lesions. In advanced stages, only DNA testing can confirm the diagnosis of STGD.

[Optical coherence tomography and fundus autofluorescence in Best macular dystrophy]. / Aspects tomographiques et en autofluorescence du fond d'œil dans la maladie de Best.

Best vitelliform macular dystrophy is the second most frequent hereditary maculopathy, with bilateral involvement and juvenile onset. It is clinically characterized by bilateral deposits of lipofuscin-like autofluorescent material in the subretinal space, with a typical phenotypic manifestation taking the form of a vitelliform macular lesion evolving gradually into more advanced stages. The purpose of our study was to describe fundus autofluorescence patterns and OCT findings in three patients (6 eyes) with several stages of Best vitelliform macular dystrophy. Optical coherence tomography (OCT) has become the first imaging technique to order when confronted with a hereditary maculopathy suggesting Best disease. Fundus autofluorescence combined with OCT allow for better diagnosis and management, which are necessary for any genetic analysis.

[Genotype-phenotype correlation in ten Tunisian families with non-syndromic retinitis pigmentosa]. / Corrélations phénotype-génotype de la rétinopathie pigmentaire non syndromique : à propos de dix familles tunisiennes.

PURPOSE: To evaluate the clinical phenotype of ten Tunisian families with non-syndromic retinitis pigmentosa (RP), to characterize genes and mutations causing these conditions, and to elaborate phenotype-genotype correlations. METHODS: Descriptive clinical genetic study of 114 individuals, of whom 27 are affected by non-syndromic RP. Ophthalmic examination and various visual tests were performed. DNA was analyzed using single nucleotide polymorphism, microsatellite genotyping and direct sequencing to determine the genes and mutations involved. RESULTS: We identified seven mutated genes: RPE65, RDH12, USHER 2A, PDE6a, PDE6b, CRB1, and NR2E3. Analysis of phenotype-genotype correlation indicated that some genes were associated with specific phenotypes. In RPE65 mutations, we found early onset dystrophy, nystagmus, keratoconus, white dot deposits in earlier stages and clumped pigment in later stages. The RDH12-associated phenotype (juvenile RP) showed severe and early-onset dystrophy, diffuse spicule pigmentation, macular edema and thickening, and tomographic re-organization of retinal layers. The CRB1 mutation was characterized by preserved para-arteriolar retinal pigment epithelium and no hemeralopia. CONCLUSION: RP is clinically and genetically heterogeneous. The two ultimate goals of research are to provide efficient clinical diagnostic of affected gene by phenotype-genotype correlation and to design novel treatment regimens. Our goal is to create a specific chip for our population, and then future research will focus on the identification of the remaining causal genes, the elucidation of the molecular mechanisms of disease in the retina and the development of gene therapy approaches.

[Foveal choroidal thickness assessment with SD-OCT in high myopic glaucoma]. / Épaisseur choroïdienne fovéolaire en OCT-SD dans le glaucome du myope fort.

PURPOSE: To measure macular choroidal thickness (CT) using spectral domain optical coherence tomography (OCT) in high myopic eyes with primary angle-open glaucoma (POAG), and to investigate whether the choroid is thinner in these eyes compared to high myopic eyes without glaucoma. PATIENTS AND METHODS: We conducted a cross-sectional study of forty-eight eyes with high myopic glaucoma matched with 48 highly myopic eyes without glaucoma by age, central corneal thickness and axial length (AL). OCT scans were performed with the spectral domain OCT (Topcon 2000). The subfoveal CT was measured between the Bruch membrane and the internal aspect of the sclera. RESULTS: In the subgroup without glaucoma, matched with the subgroup with glaucoma (P=0.57), by age, central corneal thickness (P=0.33) and AL (P=0.10), the mean subfoveal CT was 96.32 µm ± 39.56 µm. In the subgroup with glaucoma, the mean subfoveal CT was 50.44 µm ± 16.36 µm. The comparison between the two subgroups found a statistically significant difference in subfoveal CT (P<10(-4)). CONCLUSIONS: Foveal choroidal thickness is reduced in highly myopic eyes with glaucoma. The choroidal thinning can be a useful parameter for the diagnosis and the follow-up of highly myopic patients with glaucoma.