Outer retinal and choriocapillaris modifications in choroideremia: three differentially impaired retinal regions and the potential diagnostic role of the external limiting membrane.

BACKGROUND: The external limiting membrane (ELM) is formed by the apical processes of Müller cells attached to the inner segments of the photoreceptor cells. Both cells are implicated in the pathogenesis of choroideremia (CHM). The purpose of this study was to explore the diagnostic role of ELM in CHM. METHODS: The study was designed as observational case series. Sixteen CHM eyes were examined by multimodal imaging and were compared to healthy controls. The main outcome was the measurement of ELM thickness and reflectivity over the follow-up, and its relationship with other multimodal imaging quantitative parameters. RESULTS: Baseline ELM was characterized by 11 ± 1 µm of thickness and 0.68 ± 0.13 of reflectivity, resulting 8 ± 1 µm (p < 0.01) and 0.65 ± 0.14 (p > 0.05) at the last follow-up. Choriocapillaris (CC) analysis revealed 3 regions. The first was characterized by normal vessel density (VD). The second surrounding the partially preserved islet, showing significantly lower baseline VD and undergoing minor changes over the follow-up. The third was localized in the partially preserved islet, showing significantly lower VD at baseline, and resulted atrophic at the last follow-up. ELM reflectivity and ELM thickness correlated both with outer retinal atrophy progression and the CC status. CONCLUSIONS: ELM may be considered a useful imaging biomarker in CHM. Its assessment confirmed a primary role of Müller cells impairment in the pathogenesis of CHM.

Choroidal Modifications Preceding the Onset of Macular Neovascularization in Age-Related Macular Degeneration.

INTRODUCTION: Macular neovascularization (MNV) is a common complication of age-related macular degeneration (AMD). Although several biomarkers may help to estimate the risk of MNV onset, neovascular complication is difficult to predict. Previous studies showed that the quantitative assessment of choroidal and choriocapillaris changes is useful for the assessment of atrophy expansion. On the other hand, scant data are available regarding the role of this kind of assessment in the setting of MNV. The aim of the study is to analyze choroidal and choriocapillaris changes occurring before the onset of MNV in patients affected by AMD using quantitative optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: The study was designed as a retrospective case series. Patients affected by AMD, categorized in eyes complicated by MNV and eyes not developing MNV, were retrospectively analyzed for 1 year of follow-up. Choroidal thickness (CT), Sattler layer thickness (SLT) and Haller layer thickness (HLT) were measured on OCT scans. Vessel density (VD) and choriocapillaris (CC) porosity were quantified on OCTA reconstructions. The main outcome measure was the relationship between choroidal and CC parameters, and MNV onset. RESULTS: We included 50 eyes of 50 AMD patients (28 male; mean age 74 ± 5 years). Over the 1-year follow-up, 15/50 eyes developed MNV (9 type 1; 3 type 2; 3 mixed type 1-2). Mean best-corrected visual acuity (BCVA) was 0.15 ± 0.15 logMAR at baseline, remaining stable in eyes not developing MNV (0.15 ± 0.12 logMAR; p > 0.05), and worsening to 0.38 ± 0.20 logMAR in eyes developing MNV (p < 0.01). VD values were similar between eyes developing MNV and eyes not complicated by MNV at baseline, with significant worsening detected only in MNV eyes. CC porosity was significantly higher in MNV eyes already before the onset of MNV. Furthermore, SLT was significantly lower in eyes developing MNV. The onset of MNV was preceded by a significant increase in intraretinal hyperreflective foci, whereas choroidal hyperreflective foci showed no evident changes. CONCLUSIONS: The degeneration of CC and the SLT thinning represent early an biomarker of MNV onset in AMD.

Choroidal neovascularization complicating sclerochoroidal calcifications.

PURPOSE: Sclerochoroidal calcifications (SCC) are rare conditions characterized by unifocal or multifocal well-defined scleral deposits of calcium. The present study describes two cases of SCC complicated by the onset of choroidal neovascularization (CNV). METHOD: Five patients affected by SCC were enrolled in the study and two cases were complicated by CNV. Both patients underwent complete ophthalmic examination with multimodal imaging including optical coherence tomography angiography (OCTA). RESULTS: In the two patients with CNV (1 male), BCVA was 20/40 and 20/50 in the affected eyes. Fundus examination revealed an irregular yellow-white lesion close to the superotemporal arcade in both patients, with exudation. The diagnosis of CNV was performed by means of fluorescein angiography in one patient and OCTA in the other patient. The patients received a total of 3 and 9 ranibizumab injections respectively over a six-year follow-up, reaching a final BCVA of 20/25 in both patients with stabilization of the CNV. CONCLUSIONS: SCC may be complicated by CNV, with good management obtained by intravitreal anti-VEGF injections.

Outer retinal tubulation formation and clinical course of advanced age-related macular degeneration.

Outer retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease's severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and Müller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5 ± 0.5 LogMAR, decreasing to 0.9 ± 0.5 LogMAR at the 3-year follow-up (p < 0.01). We detected completely formed ORT in 26/70 eyes (37%), subdivided as follows: 20 eyes (77%) wet AMD and 6 eyes (23%) dry AMD (p < 0.01). ORT took 18 ± 8 months (range 3-35 months) to develop fully. We described the steps leading to ORT development, characterized by progressive involvement of, and damage to the photoreceptors, the ELM and the RPE. Eyes displaying ORT were associated with a smaller QDAF area, less retinal layers damage and lower rate of foveal sparing than eyes free of ORT (p < 0.01). We also described pigment accumulations simulating ORT, which were detected in 16/70 eyes (23%), associated with a greater loss of foveal sparing, increased DDAF area and smaller QDAF area at the 3-year follow-up (p < 0.01). In conclusion, this study provided a description of the steps leading to ORT development in AMD. ELM and Müller cells showed a role in ORT pathogenesis. Furthermore, we described a subtype of pigment hypertrophy mimicking ORT, evaluating its clinical utility.

Real-Life Management of Central and Branch Retinal Vein Occlusion: A Seven-Year Follow-Up Study.

Retinal vein occlusion is the second most common retinal vascular pathology after diabetic retinopathy and a major cause of vision impairment. Nowadays, both central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) can be well-managed by intravitreal treatments. However, considering the long-life expectance of the patients, few data are present in the literature about the very long-term outcome of CRVO and BRVO. The present study was an interventional, retrospective analysis of the morphological and functional long-term outcome of CRVO and BRVO patients, followed in an Italian referral center. We collected data from 313 eyes (178 CRVO eyes and 135 BRVO eyes). Mean follow-up was 45 ± 25 months (range 12-84 months). Both CRVO and BRVO eyes experience a significant visual acuity improvement secondary to anti-vascular endothelial growth factor/dexamethasone treatments (from 0.57 ± 0.25 to 0.41 ± 0.24 LogMAR in CRVO and from 0.53 ± 0.42 to 0.30 ± 0.41 LogMAR in BRVO, respectively) (p < 0.01). Also, central macular thickness (CMT) resulted significant recovery at the end of the follow-up (from 585.54 ± 131.43 to 447.88 ± 245.07 µm in CRVO and from 585.54 ± 131.43 to 447.88 ± 245.07 µm in BRVO, respectively) (p < 0.01). CRVO eyes received a mean of 10.70 ± 4.76 intravitreal treatments, whereas BRVO underwent 9.80 ± 5.39 injections over the entire 7-year follow-up. Our analyses highlighted different time points indicating the best obtainable improvement. This was the first year for CRVO (12-month follow-up) and the second year for BRVO (24-month follow-up). After these two time points, both visual acuity and CMT resulted stable up to the end of the follow-up. Ischemia was associated with significantly worse outcome.