Sectorial Ganglion Cell Complex Thickness as Biomarker of Vision Outcome in Patients With Dominant Optic Atrophy.

Purpose: Dominant optic atrophy (DOA) is an inherited condition caused by autosomal dominant mutations involving the OPA-1 gene. The aim of this study was to assess the relationship between macular ganglion cell and inner plexiform layer (GC-IPL) thickness obtained from structural optical coherence tomography (OCT) and visual outcomes in DOA patients. Methods: The study recruited 33 patients with confirmed OPA-1 heterozygous mutation and DOA. OCT scans were conducted to measure the GC-IPL thickness. The average and sectorial Early Treatment Diabetic Retinopathy Study (ETDRS) charts (six-sector macular analysis to enhance the topographical analysis) centered on the fovea were considered. Several regression analyses were carried out to investigate the associations between OCT metrics and final best-corrected visual acuity (BCVA) as the dependent variable. Results: The mean BCVA was 0.43 ± 0.37 logMAR, and the average macular GC-IPL thickness was 43.65 ± 12.56 µm. All of the GC-IPL sectors were significantly reduced and correlated with BCVA. The univariate linear regression and the multivariate stepwise regression modeling showed that the strongest association with final BCVA was observed with the internal superior GC-IPL thickness. Dividing patients based on BCVA, we found a specific pattern. Specifically, in patients with BCVA ≤ 0.3 logMAR, the external superior and inferior sectors together with the internal superior were more significant; whereas, for BCVA > 0.3 logMAR, the external superior sector and internal superior sector were more significant. Conclusions: The study identified OCT biomarkers associated with visual outcomes in DOA patients. Moreover, we assessed a specific OCT biomarker for DOA progression, ranging from patients in the early stages of disease with more preserved GC-IPL sectorial thickness to advanced stages with severe thinning.

Peripapillary hyperreflective ovoid mass-like structures (PHOMS) in patients with acute Leber's hereditary optic neuropathy.

PURPOSE: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) represent an optical coherence tomography (OCT) finding that has been characterized in different forms of pseudopapilledema. The aim of this study was to investigate the prevalence of PHOMS in patients affected by acute LHON using structural OCT, and to provide a detailed description of these findings. METHODS: Patients with a clinical and molecularly confirmed diagnosis of acute LHON (visual loss having occurred less than 6 months) were enrolled from the neuro-ophthalmology clinic at San Raffaele Scientific Institute. Patients had a complete ophthalmologic evaluation, including imaging with structural OCT. RESULTS: Our analysis included 16 patients (21 eyes-8 males and 8 females) with acute LHON. Structural OCT exhibited PHOMS in 12 eyes from 9 patients with a prevalence rate of 57.1%. In a subsequent topographical assessment in the peripapillary area, the most common location of PHOMS was the temporal region (12 out of 12 eyes), while the nasal region was affected in 2 eyes (16.7%). Considering the 12 eyes with PHOMS, mean ± SD temporal peripapillary RNFL thickness was 87.5 ± 28.4 microns. The temporal peripapillary RNFL thickness was significantly lower in eyes without PHOMS (63.7 ± 32.2 microns; P = 0.40). At the 12-month follow-up visit, PHOMS disappeared in 10 out of 12 eyes. CONCLUSIONS: Acute LHON eyes have PHOMS which are mainly confined to the temporal peripapillary sector. PHOMS may represent swelled retinal fibers that have herniated or are in stasis.

Retinal Thickness Deviation: A New OCT Parameter for Assessing Diabetic Macular Edema.

(1) Purpose: To determine the "retinal thickness deviation" (RTD) in diabetic macular edema (DME) eyes treated with intravitreal therapy and to establish associations between RTD and best-corrected visual acuity (BCVA). (2) Methods: We conducted a retrospective study, including consecutive patients with DME eyes undergoing intravitreal therapy with two years of follow-up. BCVA and central subfield thickness (CST) were collected at baseline and at 12 months and 24 months of follow-up. RTD was calculated as the absolute difference between measured and normative CST values at each time point. Linear regression analyses were performed between RTD and BCVA and between CST and BCVA. (3) Results: One hundred and four eyes were included in the analysis. The RTD was 177.0 (117.2) µm at baseline, 97.0 (99.7) µm at 12 months and 89.9 (75.3) µm at 24 months of follow-up (p < 0.001). RTD showed a moderate association with BCVA at baseline (R2 = 0.134, p < 0.001) and 12 months (R2 = 0.197, p < 0.001) and a substantial association at 24 months (R2 = 0.272, p < 0.001). The CST showed a moderate association with BCVA at baseline (R2 = 0.132, p < 0.001) and 12 months (R2 = 0.136, p < 0.001), while the association was weak at 24 months (R2 = 0.065, p = 0.009). (4) Conclusions: RTD showed a good association with visual outcome in patients with DME eyes undergoing intravitreal treatment.

Capturing the Transition From Intermediate to Neovascular AMD: Longitudinal Inner Retinal Thinning and Factors Associated With Neuronal Loss.

Purpose: To estimate the impact of transition from intermediate to exudative neovascular age-related macular degeneration (AMD) on the inner retina and to assess the relationship of clinical characteristics and optical coherence tomography (OCT) findings with inner retinal changes. Methods: A total of 80 participants (80 eyes) with intermediate AMD at baseline who developed neovascular AMD within 3 months were included in the analysis. OCT scans at follow-up visits (after transition to neovascular AMD) were compared with values at the latest visit with evidence of intermediate AMD to quantify longitudinal inner retinal changes. OCT images were also reviewed for qualitative features reflecting distress of the outer retina or retinal pigment epithelium and for the presence and characteristics of exudation. Results: The parafoveal and perifoveal inner retinal thicknesses were 97.6 ± 12.9 µm and 103.5 ± 16.2 µm, respectively, at baseline, and a significant increase in values was detected at the visit with first evidence of neovascular AMD (parafoveal: 99.0 ± 12.8 µm, P = 0.040; perifoveal: 107.9 ± 19.0 µm, P = 0.0007). Conversely, the inner retina was significantly thinner at the 12-month follow-up visit after initiation of the anti-vascular endothelial growth factor therapy (parafoveal: 90.3 ± 14.8 µm, P < 0.0001; perifoveal: 92.0 ± 21.3 µm, P < 0.0001). At the 12-month follow-up visit, OCT evidence of alterations of the external limiting membrane and history of previous intraretinal fluid were associated with a greater inner retinal thinning. Conclusions: The development of exudative neovascularization is associated with significant neuronal loss that may be detected once the exudation is resolved. OCT analysis demonstrated a significant relationship between morphological alterations detected using structural OCT and the amount of inner neuronal loss.

CLINICAL CHARACTERISTICS AND MULTIMODAL IMAGING FINDINGS IN UNILATERAL FROSTED BRANCH ANGIITIS: A CASE REPORT.

PURPOSE: Our aim is to report a comprehensive multimodal imaging case of unilateral frosted branch angiitis in a 40-years-old Caucasian female . METHODS: Case report involving clinical examination, ultra- wide field fundus photograph, ultra-wide field fluorescein angiography (UWFA), optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). RESULTS: A 40 years old patients presented with unilateral acute vision loss. On fundus examination, extensive retinal veins sheathing, macular edema and vascular congestion were observed while UWFA revealed an hyperfluorescent "hot" optic disc and blood retinal barrier disruption. OCTA displayed foveal avascular zone (FAZ) enlargement and excluded papillary neovascularization. Extensive laboratory work-up for infectious, autoimmune and inflammatory disorders were negative, thus, a diagnose of acute idiopathic unilateral frosted branch angiitis was made. Intravitreal injection of dexamethasone implant was administered with a good clinical response. CONCLUSIONS: Multimodal imaging is crucial to correctly diagnose and treat FBA. Up to our knowledge, the use of OCTA as a complementary tool to the diagnostic process in FBA has been described in literature just once as a photo essay of cytomegalovirus-related FBA and it might be of great value for better characterizing clinical features of this disorder and for following disease activity in a non-invasive fashion.

Choroidal vascularity index in hereditary optic neuropathies.

PURPOSE: To assess the choroidal vascularity index (CVI) in patients affected by Leber hereditary optic neuropathy (LHON) compared to patients affected by dominant optic atrophy (DOA) and healthy subjects. METHODS: In this retrospective study, we considered three cohorts: LHON eyes (48), DOA eyes (48) and healthy subjects' eyes (48). All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) acquisition. OCT parameters as subfoveal choroidal thickness (Sub-F ChT), mean choroidal thickness (ChT), total choroidal area (TCA), luminal choroidal area (LCA) were calculated. CVI was obtained as the ratio of LCA and TCA. RESULTS: Subfoveal ChT in LHON patients did not show statistically significant differences compared to controls, while in DOA a reduction in choroidal thickness was observed (p = 0.344 and p = 0.045, respectively). Mean ChT was reduced in both LHON and DOA subjects, although this difference reached statistical significance only in DOA (p = 0.365 and p = 0.044, respectively). TCA showed no significant differences among the 3 cohorts (p = 0.832). No changes were detected in LCA among the cohorts (p = 0.389), as well as in the stromal choroidal area (SCA, p = 0.279). The CVI showed no differences among groups (p = 0.898): LHON group was characterized by a similar CVI in comparison to controls (p = 0.911) and DOA group (p = 0.818); the DOA group was characterized by a similar CVI in comparison to controls (p = 1.0). CONCLUSION: CVI is preserved in DOA and LHON patients, suggesting that even in the chronic phase of the neuropathy the choroidal structure is not irreversibly compromised.

Imaging biomarkers and clinical factors associated with the rate of progressive inner and outer retinal thinning in patients with diabetic macular edema.

The aim of this study was to assess the relationship of clinical characteristics to the rate of retinal thinning in eyes with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (VEGF) therapy. We analyzed subjects with a long-term follow-up (≥ 3 years) and evidence of resolved DME after the initiation of anti-VEGF therapy (baseline visit). To measure the long-term rate of retinal thinning during treatment, a second visit (first visit with evidence of resolved DME after 3 years) was also considered. A longitudinal quantitative topographical assessment of the inner and outer retinal thicknesses was provided. Clinical characteristics were associated with the rate of longitudinal retinal thinning. We included 56 eyes (50 patients) in the analysis. A significant longitudinal thinning in the inner and outer retina was detected in all the analyzed regions (p values between 0.027 and < 0.0001). In the multivariable analysis, type of diabetes (type 2 vs. type 1) was associated with increased foveal inner retinal thinning (p = 0.019). A higher number of subfoveal neuroretinal detachment during follow-up (p = 0.006) was associated with faster rates of foveal outer retinal thinning. Type of diabetes (p < 0.0001), higher age (p = 0.033) and cystoid macular edema phenotype (p = 0.040) were associated with increased parafoveal inner retinal thinning. Gender (p = 0.003) and diabetic retinopathy stage (p = 0.013) were associated with faster rates of perifoveal inner retinal thinning, while diabetic retinopathy stage (p = 0.036) was associated with increased perifoveal outer retinal thinning. In conclusion, clinical factors, including DME phenotypes, were associated with the rates of retinal thinning in patients undergoing anti-VEGF treatment.

Visual Outcomes and Optical Coherence Tomography Biomarkers of Vision Improvement in Patients With Leber Hereditary Optic Neuropathy Treated With Idebenone.

PURPOSE: To assess the relationship of demographics, clinical characteristics and structural optical coherence tomography (OCT) findings to long-term visual outcomes in patients with Leber hereditary optic neuropathy (LHON) treated with idebenone. DESIGN: Retrospective, interventional, noncomparative clinical cohort study. METHODS: In this study, a total of 17 participants (34 eyes) with LHON treated with idebenone therapy within 1 year after disease onset and 2 years (24 months) of regular follow-ups were retrospectively enrolled. At baseline, structural OCT volume scans of the macula and optic nerve were reviewed to measure metrics reflecting neuronal loss (ie, macular ganglion cell and inner plexiform layer [GC-IPL] and peripapillary retinal nerve fiber layer [RNFL] thicknesses). Stepwise multiple regression analyses were computed to assess associations between final best-corrected visual acuity (BCVA) at 2 years and change in BCVA from baseline at 2 years as dependent variables with demographics, clinical characteristics, and OCT metrics at baseline (visit before the initiation of treatment). RESULTS: The BCVA was 1.6±0.8 logMAR (Snellen VA of ∼20/800) at baseline (visit before the initiation of treatment) and 1.0±0.7 logMAR (Snellen VA of 20/200) at the 2-year follow-up visit (P < .0001). Mean±SD change in BCVA from baseline at 2 years was -51.9%±35.9%. In multivariable analysis, the strongest associations with final BCVA were with baseline BCVA (P = .012), superior macular GC-IPL thickness (P = .044), superotemporal macular GC-IPL thickness (P = .010), and inferotemporal macular GC-IPL thickness (P = .015). Similarly, the strongest associations with delta BCVA were with superior macular GC-IPL thickness (P = .045), superotemporal macular GC-IPL thickness (P = .047), and inferotemporal macular GC-IPL thickness (P = .030). CONCLUSION: We identified OCT biomarkers associated with long-term (ie, 2-year) visual outcomes in patients with LHON treated with idebenone therapy in the first year after disease onset. Thinning of the GC-IPL in the superior and temporal parafoveal regions was associated with worse long-term visual outcomes in these patients.

Long-Term Visual Outcomes and Morphologic Biomarkers of Vision Loss in Eyes With Diabetic Macular Edema Treated With Anti-VEGF Therapy.

PURPOSE: To analyze the morphological characteristics and long-term visual outcomes in eyes with diabetic retinopathy (DR) and diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. DESIGN: Retrospective clinical cohort study. METHODS: Patients with a long-term follow-up and evidence of resolved DME in at least 1 visit (study visit) after 5 years of follow-up after the initiation of anti-VEGF therapy were included. At the study visit, structural optical coherence tomography (OCT) scans were reviewed for qualitative features reflecting a distress of the neuroretina or retinal pigment epithelium (RPE). A quantitative topographical assessment of the inner and outer retinal thicknesses was also provided. RESULTS: A total of 61 eyes (50 patients) were included and were divided into 2 subgroups according to visual acuity (VA) at the study visit, yielding a group of 24 eyes with a VA <20/40 ("poor/intermediate vision" group), and 37 eyes with a VA ≥20/40 ("good vision" group). The external limiting membrane (ELM) and RPE bands were more frequently disrupted or absent in the poor/intermediate vision group (P = .003 and P = .019). Similarly, disorganization of retinal inner layers was more prevalent in the poor/intermediate vision group (P = .013). The foveal and parafoveal outer retinal thicknesses were reduced in eyes with poor/intermediate vision (P = .022 and P = .044). Multivariate stepwise linear regression analysis demonstrated that VA was associated with appearances of the RPE and ELM (P < .0001 and P = .048), foveal and parafoveal outer retinal thicknesses (P = .046 and P = .035). CONCLUSIONS: Modifications in the outer retina and RPE represent OCT biomarkers of long-term visual outcomes in eyes with DME treated with anti-VEGF.