Glaucoma, a heterogeneous set of progressively degenerative optic neuropathies characterized by a loss of retinal ganglion cells (RGCs) and typical visual field deficits that can progress to ...blindness, is a neurodegenerative disease involving both ocular and visual brain structures. Although elevated intraocular pressure (IOP) remains the most important modifiable risk factor of primary open-angle glaucoma (POAG) and is the main therapeutic target in treating glaucoma, other factors that influence the disease course are involved and reaching the optimal IOP target does not stop the progression of glaucoma, as the visual field continues to narrow. In addition to a managed IOP, neuroprotection may be beneficial by slowing the progression of glaucoma and improving the visual defects. Citicoline (cytidine 5'-diphosphocholine) is a naturally occurring endogenous compound that has been investigated as a novel therapeutic agent for the management of glaucoma. Citicoline has demonstrated activity in a range of central neurodegenerative diseases, and experimental evidence suggests a it performs a neuromodulator and neuroprotective role on neuronal cells, including RGCs, associated with improvement in visual function, extension of the visual field and central benefits for the patient. This review aims to critically summarize the current evidence for the neuroprotective properties of citicoline in glaucoma.
To analyze the quantitative and qualitative early changes of choroidal neovascularization (CNV) associated with chronic central serous chorioretinopathy (CSC) after treatment using optical coherence ...tomography-angiography (OCT-A).
Charts of consecutive patients with diagnosis of chronic CSC complicated by CNV were retrospectively reviewed. Included patients were divided in photodynamic therapy (PDT) or aflibercept group on the basis of the treatment received (half-fluence PDT or aflibercept 2.0 mg/0.05 ml intravitreal injection). Main outcome measures included the changes between baseline and 1-month follow-up in CNV vessel density (VD) and area on OCT-A images after thresholding and binarization.
A total of 30 eyes of 26 Caucasian patients were included: 17 eyes of 15 patients in PDT group (mean age 53 ± 11 years) and 13 eyes of 11 patients in aflibercept group (mean age 58 ± 8 years p = 0.196). In both PDT and aflibercept groups, best-corrected visual acuity improved at 1 month, and central macular thickness and subretinal fluid significantly decreased. VD did not change after the treatment in both groups (p = 0.502 and p = 0.086) although CNV area decreased significantly (from 0.586 ± 0.449 mm
to 0.553 ± 0.453 mm
0.041) in the PDT group, and nonsignificantly (from 0.767 ± 0.466 mm
to 0.733 ± 0.472 mm
p = 0.095) in the aflibercept group. The same results were confirmed in the subanalysis of the 18 treatment-naïve eyes.
We demonstrated that, despite all patients showed a favorable clinical response, VD of CNVs complicating chronic CSC did not change after treatment. These findings support the idea that arteriogenesis is the main driving force of CNV in pachychoroid-related macular disorders.
To compare the performance of two different spectral-domain optical coherence tomography angiography (OCTA) devices in clinical practice by evaluating examination execution time and the number of ...motion artifacts per image.
Seventy-six patients affected by different ocular diseases and 13 healthy subjects consecutively underwent assessments by two different OCTA devices: AngioPlex (Zeiss Meditec, Inc., Dublin, Calif., USA) and AngioVue (OptoVue, Inc., Fremont, Calif., USA). Two different operators (L.A.D.V. and L.B.) measured execution times, excluded low-quality images, and counted the number of motion artifacts per image.
The mean execution time was shorter with AngioPlex than with AngioVue for all subjects (3 min 32 s ± 1 min 45 s vs. 4 min 35 s ± 1 min 11 s; p < 0.0001), for the healthy subjects (2 min 31 s ± 45 s vs. 4 min 1 s ± 53 s; p = 0.003), and for the patients (3 min 44 s ± 1 min 48 s vs. 4 min 42 s ± 1 min 13 s; p < 0.0001). The percentages of available images, low-signal-strength images, and images impossible to analyze of the total acquired images obtained using AngioPlex or AngioVue were 85, 6, and 9% and 56, 29, and 15%, respectively. The mean number of motion artifacts was significantly lower in images obtained using AngioPlex than in images obtained using AngioVue for all patients (6.5 ± 5.9 vs. 12.6 ± 8.5; p < 0.0001), for the healthy subjects (6.5 ± 4.6 vs. 10.9 ± 7.9; p = 0.0009), and for the patients (6.6 ± 6.3 vs. 13.1 ± 8.7; p < 0.0001). There was no correlation between the number of artifacts and execution time or patients' age.
AngioPlex and AngioVue are useful devices in clinical practice. AngioPlex requires a shorter execution time and provides a higher number of images available for analysis with fewer motion artifacts.
Aims
To analyze retinal vascular plexuses and choriocapillaris by optical coherence tomography angiography (OCT-A) and retinal nerve fiber layer and ganglion cell layer (GCL) by structural optical ...coherence tomography (OCT) in patients with type 1 diabetes mellitus (T1DM) without diabetic retinopathy (DR).
Methods
A total of 25 eyes of 25 consecutive T1DM patients without signs of DR were prospectively recruited and compared to 25 healthy subjects (control eyes). All patients underwent OCT-A (CIRRUS HD-OCT model 5000, Carl Zeiss Meditec, Dublin, CA) and structural OCT. Qualitative and quantitative analyses with vessel density were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris for all patients.
Results
By means of OCT-A, a rarefaction of the perifoveal capillary network in SCP was detected in 7 out of 25 eyes. No significant difference was found in FAZ area of both SCP and DCP comparing diabetic and control groups. By analyzing the DCP, diabetic eyes revealed a significant decreased vessel density compared to control eyes 0.464 ± 0.016 and 0.477 ± 0.014, respectively (
p
= 0.005). Instead, no significant difference was found in the vessel density of all-retina plexus, SCP and choriocapillaris. By RFNL and GCL thickness analysis, no significant differences were disclosed between diabetics and healthy subjects.
Conclusions
We demonstrated the ability of OCT-A to disclose early vascular alterations in patients with T1DM diagnosed as without any signs of DR on the basis of fundus biomicroscopy. Our results also suggest that microvascular changes could precede detectable damage of diabetic neuroretinopathy.
Purpose: In LEROS, visual acuity (VA) outcomes in idebenone‐treated patients with LHON were compared to an external, matched, natural history (NH) cohort. Here, we report results from a cumulative ...frequency analysis to understand the impact of idebenone on carriers of each of the primary mitochondrial DNA (mtDNA) mutations.
Methods: Patients with LHON and a confirmed primary mtDNA mutation (11 778, 14 484 or 3460) were enrolled and stratified by time since onset: acute (≤1 year) and chronic (>1 but ≤5 years). Data from 181 patients treated up to 24 months were compared to retrospective data from the NH cohort (372 patients), matched by time since onset. In a cumulative frequency analysis, VA change was assessed from baseline to month 24. A change of ≥0.2 logMAR was considered a clinically relevant recovery or worsening, depending on the direction of change.
Results: For carriers of the 11 778 mutation, VA outcomes were observed, in treated versus untreated eyes, as follows: recovery: 38.3% (23/60) vs. 14.9% (7/47) acute, 24.4% (20/82) vs. 13.7% (7/51) chronic; worsening: 24.4% (10/41) vs. 66.7% (20/30) acute, 4.4% (2/45) vs. 31.6% (6/19) chronic. For 14 484 carriers VA outcomes were as follows: recovery: 74.3% (26/35) vs. 70.0% (7/10) acute, 90.9% (10/11) vs. 16.7% (3/18) chronic; worsening: 2.9% (1/35) vs. 22.2% (2/9) acute, 0.0% (0/8) vs. 16.7% (3/18) chronic. For 3460 carriers, outcomes were as follows: recovery: 34.6% (9/26) vs. 61.1% (11/18) acute, and 30.4% (7/23) vs. 20.8% (5/24) chronic; worsening: 76.5% (13/17) vs. 30.0% (3/10) acute, and 0.0% (0/15) vs. 13.0% (3/23) chronic.
Conclusions: Idebenone can improve the ratio of positive to negative VA outcomes in a large proportion of patients with LHON, although these benefits seem to manifest to varying degrees dependent on disease stage and/or causative mtDNA mutation. Carriers of the most prevalent mutation, 11 778, saw a consistent treatment benefit regardless of disease stage.
Purpose: For patients with LHON, preservation of functional visual acuity (VA) and/or recovery of lost VA are desirable outcomes. Beyond this, prevention of further VA worsening is also important. In ...LEROS, VA outcomes following 24 months of idebenone treatment were compared to an external, matched, natural history (NH) cohort. Here, we report results from a cumulative frequency analysis to understand the impact of idebenone across the range of possible VA outcomes.
Methods: Patients with LHON onset ≤5 years prior were enrolled and stratified by time since onset: subacute/dynamic (≤1 year) and chronic (>1 year). Data from 181 patients treated up to 24 months were compared to retrospective data from an external natural history (NH) cohort (372 patients), matched by time since onset. In a cumulative frequency analysis, VA change was assessed from baseline to month 24. A change of ≥0.2 logMAR was considered a clinically relevant recovery or worsening, depending on the direction of change.
Results: In subacute/dynamic eyes treated with idebenone for 24 months, 47.9% (58/121) experienced a recovery of VA, and 25.8% (24/93) experienced VA worsening. This compared to 33.3% (25/75), and 51.0% (25/49) of untreated subacute/dynamic eyes displaying a recovery or worsening, respectively. In chronic eyes, recovery was observed in 31.9% (37/116) that had undergone treatment versus 16.1% (15/93) when untreated. A VA worsening was observed for 2.9% (2/68) of treated chronic eyes versus 20.0% (12/60) of untreated. The majority of treatment emergent adverse events were considered of mild to moderate intensity, with only 11.3% considered to be related to idebenone treatment.
Conclusions: In both the subacute/dynamic and chronic stages of LHON, idebenone treatment was able to boost VA recovery and prevent further VA deterioration. Consistent with previous findings, idebenone was well tolerated with no new safety concerns observed.
Purpose: For patients with LHON, preservation of functional visual acuity (VA) and/or recovery of lost VA are desirable outcomes. Beyond this, prevention of further VA worsening is also important. In ...LEROS, VA outcomes following 24 months of idebenone treatment were compared to an external, matched, natural history (NH) cohort. Here, we report results from a cumulative frequency analysis to understand the impact of idebenone across the range of possible VA outcomes.Methods: Patients with LHON onset ≤5 years prior were enrolled and stratified by time since onset: subacute/dynamic (≤1 year) and chronic (>1 year). Data from 181 patients treated up to 24 months were compared to retrospective data from an external natural history (NH) cohort (372 patients), matched by time since onset. In a cumulative frequency analysis, VA change was assessed from baseline to month 24. A change of ≥0.2 logMAR was considered a clinically relevant recovery or worsening, depending on the direction of change.Results: In subacute/dynamic eyes treated with idebenone for 24 months, 47.9% (58/121) experienced a recovery of VA, and 25.8% (24/93) experienced VA worsening. This compared to 33.3% (25/75), and 51.0% (25/49) of untreated subacute/dynamic eyes displaying a recovery or worsening, respectively. In chronic eyes, recovery was observed in 31.9% (37/116) that had undergone treatment versus 16.1% (15/93) when untreated. A VA worsening was observed for 2.9% (2/68) of treated chronic eyes versus 20.0% (12/60) of untreated. The majority of treatment emergent adverse events were considered of mild to moderate intensity, with only 11.3% considered to be related to idebenone treatment.Conclusions: In both the subacute/dynamic and chronic stages of LHON, idebenone treatment was able to boost VA recovery and prevent further VA deterioration. Consistent with previous findings, idebenone was well tolerated with no new safety concerns observed.
Purpose: In LEROS, visual acuity (VA) outcomes in idebenone‐treated patients with LHON were compared to an external, matched, natural history (NH) cohort. Here, we report results from a cumulative ...frequency analysis to understand the impact of idebenone on carriers of each of the primary mitochondrial DNA (mtDNA) mutations.Methods: Patients with LHON and a confirmed primary mtDNA mutation (11 778, 14 484 or 3460) were enrolled and stratified by time since onset: acute (≤1 year) and chronic (>1 but ≤5 years). Data from 181 patients treated up to 24 months were compared to retrospective data from the NH cohort (372 patients), matched by time since onset. In a cumulative frequency analysis, VA change was assessed from baseline to month 24. A change of ≥0.2 logMAR was considered a clinically relevant recovery or worsening, depending on the direction of change.Results: For carriers of the 11 778 mutation, VA outcomes were observed, in treated versus untreated eyes, as follows: recovery: 38.3% (23/60) vs. 14.9% (7/47) acute, 24.4% (20/82) vs. 13.7% (7/51) chronic; worsening: 24.4% (10/41) vs. 66.7% (20/30) acute, 4.4% (2/45) vs. 31.6% (6/19) chronic. For 14 484 carriers VA outcomes were as follows: recovery: 74.3% (26/35) vs. 70.0% (7/10) acute, 90.9% (10/11) vs. 16.7% (3/18) chronic; worsening: 2.9% (1/35) vs. 22.2% (2/9) acute, 0.0% (0/8) vs. 16.7% (3/18) chronic. For 3460 carriers, outcomes were as follows: recovery: 34.6% (9/26) vs. 61.1% (11/18) acute, and 30.4% (7/23) vs. 20.8% (5/24) chronic; worsening: 76.5% (13/17) vs. 30.0% (3/10) acute, and 0.0% (0/15) vs. 13.0% (3/23) chronic.Conclusions: Idebenone can improve the ratio of positive to negative VA outcomes in a large proportion of patients with LHON, although these benefits seem to manifest to varying degrees dependent on disease stage and/or causative mtDNA mutation. Carriers of the most prevalent mutation, 11 778, saw a consistent treatment benefit regardless of disease stage.
Abstract only
Aims/Purpose:
Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to progressive, bilateral vision loss. Childhood‐onset LHON has a relatively good prognosis, ...suggesting that age at onset influences disease progression and potential response to treatment. In LEROS, a Phase IV, open‐label interventional study (ClinicalTrials.gov NCT02774005), visual acuity (VA) outcomes following 24 months of idebenone treatment (IDE) were compared to those of a Natural History (NH) cohort.
Methods:
LEROS included patients aged ≥12 years with a disease onset ≤5 years prior. Data from 181 patients were compared to retrospective data from a NH cohort (
N
= 372), matched by time since symptom onset. Here, we compare the difference in least squares‐mean VA change, or delta VA, from baseline to Month 24 in treated eyes versus those in the NH cohort (a negative value favours IDE). Eyes were stratified by time since symptom onset at baseline: subacute/dynamic (≤1 year) and chronic (>1 year) phase, and by age at symptom onset (<18 years, ≥18 years).
Results:
In treated subacute/dynamic eyes from the <18 years group (
n
= 22 IDE), delta VA was +0.38 logMAR (
p
= 0.020) relative to the NH cohort (
n
= 22). In the chronic phase, delta VA was −0.08 logMAR (
n
= 16 IDE vs
n
= 37 NH eyes;
p
= 0.405). In subacute/dynamic eyes from the ≥18 years group, delta VA was −0.18 logMAR (
n
= 99 IDE vs
n
= 53 NH;
p
= 0.060). In the chronic phase, delta VA was −0.21 logMAR (
n
= 100 IDE vs
n
= 56 NH;
p
< 0.001).
Conclusions:
In eyes of patients ≥18 years at symptom onset, VA improvement at Month 24 was greater in idebenone‐treated versus untreated NH eyes. Treatment benefit was particularly apparent in the chronic phase, corresponding to >10 additional letters on the ETDRS chart. In subacute/dynamic eyes, spontaneous VA recovery was unexpectedly high in the NH cohort. In chronic eyes from patients <18 years, a non‐significant trend favouring idebenone was observed.
Abstract only
Aims/Purpose:
Leber hereditary optic neuropathy (LHON) is a mitochondrial disease resulting in bilateral vision loss. Childhood‐onset LHON has a relatively good prognosis, suggesting ...that age influences disease progression and, potentially, treatment response. In LEROS, a Phase IV, open‐label interventional study (Clinicaltrials.gov NCT02774005), visual acuity (VA) outcomes following 24 months of idebenone treatment (IDE) were compared to those of an external Natural History (NH) cohort.
Methods:
LEROS included patients aged ≥12 years with a disease onset ≤5 years prior. Data from 181 patients were compared to retrospective data from a NH cohort (
N
= 372), matched by time since symptom onset. Here, we compare clinically relevant recovery (CRR) and clinically relevant worsening (CRW) from baseline to Month 24 in IDE eyes versus NH eyes, stratified by time since symptom onset at baseline: subacute/dynamic (≤1 year) and chronic (>1 year) phase, and by age at symptom onset (<18 years, ≥18 years).
Results:
In patients aged <18 years, VA outcomes were observed, in IDE versus NH eyes, as follows: CRR: subacute/dynamic 31.8% (7/22) vs 59.1% (13/22),
p
= 0.048; chronic 31.3% (5/16) vs 21.6% (8/37),
p
= 0.241; CRW: subacute/dynamic 26.3% (5/19) vs 21.4% (3/14),
p
= 0.558; chronic 8.3% (1/12) vs 19.2% (5/26),
p
= 0.078. In patients aged ≥18 years, the following VA outcomes were observed: CRR: subacute/dynamic 51.5% (51/99) vs 22.6% (12/53),
p
= 0.001; chronic 32.0% (32/100) vs 12.5% (7/56),
p
< 0.001; CRW: subacute/dynamic 25.7% (19/74) vs 62.9% (22/35),
p
< 0.001; chronic 1.8% (1/56) vs 20.6% (7/34),
p
= 0.003.
Conclusions:
Idebenone improved the ratio of positive to negative VA outcomes. Treatment benefit was particularly pronounced in patients ≥18 years at onset, with only non‐significant positive trends observed in chronic patients <18 years. Results in subacute/dynamic patients aged <18 years were limited by an unusually high recovery rate in the NH cohort, warranting further study.
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