Contribution of ultra-wide field fluorescein angiography in diabetic retinopathy in a Tunisian population.

AIM: To assess the contribution of ultra-wide field (UWF) fluorescein angiography (FA) in clinically non proliferative diabetic retinopathy (DR) and to study the relationship between peripheral vascular lesions and the presence of diabetic macular edema (DME). METHODS: Retrospective study of consecutive UWF-FA obtained using a wide-field contact lens system. DME was detected on both FA and spectral-domain optical coherence tomography (SD-OCT). RESULTS: A total of 71 eyes of 39 diabetic patients with clinically non proliferative DR (NPDR) was included. DR was clinically graded as severe NPDR in 52 eyes (73%), moderate NPDR in 15 eyes (21%) and mild NPDR in 4 eyes (6%). On UWF-FA, DR was predominantly anterior in 14% of cases (10/71), predominantly posterior in 48% of cases (34/71) and diffuse in 38% of cases (27/71). Retinal non perfusion was present in 87% of eyes (62/71), predominating in superior-temporal areas. Peripheral vessel leakage was present in 85% of cases (60/71) and retinal neovascularization was noted in 14% of cases (10/71), unpgrading DR severity from NPDR to proliferative DR in 10 eyes. DME was present on SD-OCT in 53% of cases. Central macular thickness was significantly higher in eyes with retinal non-perfusion (353 µm vs. 254 µm, p=0,006) and retinal non-perfusion was associated with macular edema (97% vs. 76%, p=0,01) and poor visual acuity (p<0.001). Peripheral vessel leakage was associated with retinal non-perfusion (p<0.001) and retinal neovascularization (53% vs. 35%, p=0.01), but it was not associated with the presence of DME (p=0.449). CONCLUSION: UWF-FA was of great help assessing DR and evaluating peripheral retinal lesions in order to refine DR staging and to guide laser treatment. Besides, it allows better understanding of DME pathophysiology.

Swept Source Optical Coherence Tomography Angiography: Characteristic Findings in Type 3 Macular Neovascularization.

We report a typical illustration of Swept source OCT-Angiography (SS-OCT-A) findings in type 3 macular neovascularization(MNV) or retinal angiomatous proliferation (RAP). This is a case of a 70-year-old Caucasian male patient presenting with an exudative type 3 neovascular age-related macular degeneration. En face SS-OCT-A could non-invasively detect a tiny perifoveal circular "clew-like" high-flow neovascular lesion, visible in the deep capillary plexus, the outer retina and communicating with the choriocapillaris, with a perilesional dark halo and associated to no-flow macular cysts in the deep capillary plexus slab. En face SS-OCT-A could also highlight the presence of a telangiectatic capillary dilation in the superficial capillary plexus appearing to be at the origin of the retinal neovascularization. Cross-sectional SS-OCT-A showed an intra-retinal vertical high vascular flow within the hyper-reflective neovascular lesion, with a typical hyperreflective "kissing sign" and associated to subretinal and intraretinal fluid. In conclusion, en face OCT-A is useful tool to diagnose type 3 MNV or RAP non-invasively and associated cross-sectional OCT-A scan is very helpful highlighting the linear vascular high-flow within the retinal neovascularization.

Multimodal Imaging in Retinitis Pigmentosa: Correlations among Microvascular Changes, Macular Function and Retinal Structure.

PURPOSE: To analyze microvascular changes in patients with retinitis pigmentosa (RP) with relatively preserved visual acuity (VA), using swept source optical coherence tomography (SS-OCT) angiography to correlate results to macular function and structure. METHODS: This was a case-control study conducted over 70 eyes of 35 RP patients with relatively preserved VA. All patients underwent a complete ophthalmic examination, including SS-OCT, OCT angiography (OCT-A), fundus autofluorescence (FAF), and multifocal electroretinogram (mfERG). Thirty-four eyes of 34 healthy controls of age-, sex-, and axial length-matched (control group), were also analyzed. The main outcome measures were foveal and parafoveal vascular densities (FVDs and PFVDs) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), foveal avascular zone (FAZ) and its enlargement coefficient and their correlation with macular function (by means of VA and mfERG), and structure (by means of FAF and SS-OCT). RESULTS: In the RP group, PFVD was 25.99 ± 5.2% in the SCP and 34.47 ± 2.37% in the DCP and were significantly lower as compared to control group (P < 0.0001; P = 0.0026, respectively). Enlargement coefficient of FAZ was 1.78 ± 0.79. We found a statistically significant correlation between VA and PFVD in the DCP (P < 0.0001), FAZ disruption in the SCP (P = 0.006) and enlargement coefficient of FAZ (P = 0.01). The parafoveal DCP density was significantly correlated with P1 amplitude (P = 0.005) in rings 2, 3, 4, and 5 of the mfERG. We found a statistically significant correlation between parafoveal density in the DCP, thickness of ganglion cell complex (GCC) (P = 0.001), and the width of ellipsoid band (P = 0.041). Parafoveal SCP density was also correlated to GCC (P = 0.033). CONCLUSIONS: We showed that vascular alteration in RP begins at the level of the DCP, which affects the outer retina and leads to a narrowing of the ellipsoid. The alteration of the SCP would occur later in the evolution of the disease. Vascular changes occur early during RP and were highly correlated to retinal function and structure. OCT-A seems to be a good tool to quantify vascular network loss and could play a central role in staging, prognosis, and monitoring disease progression.

Genetic spectrum of retinal dystrophies in Tunisia.

We report the molecular basis of the largest Tunisian cohort with inherited retinal dystrophies (IRD) reported to date, identify disease-causing pathogenic variants and describe genotype-phenotype correlations. A subset of 26 families from a cohort of 73 families with clinical diagnosis of autosomal recessive IRD (AR-IRD) excluding Usher syndrome was analyzed by whole exome sequencing and autozygosity mapping. Causative pathogenic variants were identified in 50 families (68.4%), 42% of which were novel. The most prevalent pathogenic variants were observed in ABCA4 (14%) and RPE65, CRB1 and CERKL (8% each). 26 variants (8 novel and 18 known) in 19 genes were identified in 26 families (14 missense substitutions, 5 deletions, 4 nonsense pathogenic variants and 3 splice site variants), with further allelic heterogeneity arising from different pathogenic variants in the same gene. The most common phenotype in our cohort is retinitis pigmentosa (23%) and cone rod dystrophy (23%) followed by Leber congenital amaurosis (19.2%). We report the association of new disease phenotypes. This research was carried out in Tunisian patients with IRD in order to delineate the genetic population architecture.

Posterior staphylomas in non-highly myopic eyes with retinitis pigmentosa.

PURPOSE: Our aim was to highlight the presence and the frequency of posterior staphyloma (PS) in non-highly myopic retinitis pigmentosa (RP) patients and to study the relationship between PS and choroidal thickness (CT). METHODS: This was a retrospective case-control study of 77 eyes (39 patients) with RP, axial length inferior to 26 mm and clinically preserved macular area. All patients underwent fundus photography, A- and B-scan ocular ultrasonography, fundus autofluorescence (FAF) and swept source optical coherence tomography (SS-OCT). PS was defined by an outward bowing of the sclera on SS-OCT and B-scans. The relationship between the PS and SS-OCT layers thicknesses was determined. RESULTS: Over 77 RP eyes of 39 patients studied, a PS was identified in 17 eyes (22%) of nine patients. Fifteen eyes had a narrow macular staphyloma (NMS), and two eyes had a wide macular staphyloma (WMS). Mean age in this group was 34.2 years (range 19-53 years), mean axial length was 23.60 ± 0.61 mm and mean CT was 185.7 ± 71 um versus 259.7 um in eyes without PS. The staphyloma edges corresponded to area of outer retina loss on SS-OCT and were larger than the hyperautofluorescent ring on FAF. We found a significant association between PS and CT in our RP patients (p = 0.003). The mean CT was significantly thinner in PS eyes compared to eyes without staphyloma. There was no significant association between PS and with visual acuity, years of progression, retinal thickness nor FAF findings. CONCLUSIONS: PS was present in 22% of non-highly myopic eyes with RP. Narrow macular staphyloma was the most common type observed in our series. A marked thinning of the choroid was noted in PS eyes when compared to RP eyes without PS, as well as the outer retina degeneration.

Phenotypic Progression of Stargardt Disease in a Large Consanguineous Tunisian Family Harboring New ABCA4 Mutations.

To assess the progression of Stargardt (STGD) disease over nine years in two branches of a large consanguineous Tunisian family. Initially, different phenotypes were observed with clinical intra- and interfamilial variations. At presentation, four different retinal phenotypes were observed. In phenotype 1, bull's eye maculopathy and slight alteration of photopic responses in full-field electroretinography were observed in the youngest child. In phenotype 2, macular atrophy and yellow white were observed in two brothers. In phenotype 3, diffuse macular, peripapillary, and peripheral RPE atrophy and hyperfluorescent dots were observed in two sisters. In phenotype 4, Stargardt disease-fundus flavimaculatus phenotype was observed in two cousins with later age of onset. After a progression of 9 years, all seven patients displayed the same phenotype 3 with advanced stage STGD and diffuse atrophy. WES and MLPA identified two ABCA4 mutations M1: c.[(?_4635)_(5714+?)dup; (?_6148)_(6479_+?) del] and M2: c.[2041C>T], p.[R681∗]. In one branch, the three affected patients had M1/M1 causal mutations and in the other branch the two affected patients had M1/M2 causal mutations. After 9-year follow-up, all patients showed the same phenotypic evolution, confirming the progressive nature of the disease. Genetic variations in the two branches made no difference to similar end-stage disease.