Microvascular damage assessed by optical coherence tomography angiography for glaucoma diagnosis: a systematic review of the most discriminative regions

A growing number of studies have reported a link between vascular damage and glaucoma based on optical coherence tomography angiography (OCTA) imaging. This multitude of studies focused on different regions of interest (ROIs) which offers the possibility to draw conclusions on the most discriminative locations to diagnose glaucoma. The objective of this work was to review and analyse the discriminative capacity of vascular density, retrieved from different ROIs, on differentiating healthy subjects from glaucoma patients. PubMed was used to perform a systematic review on the analysis of glaucomatous vascular damage using OCTA. All studies up to 21 April 2019 were considered. The ROIs were analysed by region (macula, optic disc and peripapillary region), layer (superficial and deep capillary plexus, avascular, whole retina, choriocapillaris and choroid) and sector (according to the Garway–Heath map). The area under receiver operator characteristic curve (AUROC) and the statistical difference (p-value) were used to report the importance of each ROI for diagnosing glaucoma. From 96 screened studies, 43 were eligible for this review. Overall, the peripapillary region showed to be the most discriminative region with the highest mean AUROC (0.80 ± 0.09). An improvement of the AUROC from this region is observed when a sectorial analysis is performed, with the highest AUROCs obtained at the inferior and superior sectors of the superficial capillary plexus in the peripapillary region (0.86 ± 0.03 and 0.87 ± 0.10, respectively). The presented work shows that glaucomatous vascular damage can be assessed using OCTA, and its added value as a complementary feature for glaucoma diagnosis depends on the region of interest. A sectorial analysis of the superficial layer at the peripapillary region is preferable for assessing glaucomatous vascular damage

Noninferiority of Preservative-free Versus BAK-preserved Latanoprost-timolol Fixed Combination Eye Drops in Patients With Open-angle Glaucoma or Ocular Hypertension

Précis: Noninferiority of efficacy was demonstrated for a preservative-free latanoprost-timolol fixed combination compared with a BAK-containing formulation at 84 days after treatment in patients with open-angle glaucoma or ocular hypertension. Purpose: The purpose of this study was to compare the effect on intraocular pressure and safety of preservative-free latanoprost-timolol fixed combination (T2347) to benzalkonium chloride-preserved latanoprost-timolol fixed combination in patients with open-angle glaucoma or ocular hypertension. Methods: Phase III, randomized, parallel-group, investigator-masked study in 10 countries. A total of 242 patients aged 18 years or older with open-angle glaucoma or ocular hypertension in both eyes controlled with a preserved latanoprost-timolol fixed combination (15.7±2.4 mm Hg overall before inclusion) were randomized at day 0 with no washout period to receive the preservative-free alternative T2347 (N=127) or remain on the preserved comparator (N=115) for 84 days. Intraocular pressure changes from day 0 were measured at 9:00 am (±1 hour) on day 42 and day 84, and noninferiority of T2347 to the preserved comparator was analyzed statistically at day 84. Safety parameters were also reported. Results: The mean change in intraocular pressure from baseline to day 84 was -0.49±1.80 mm Hg for preservative-free T2347 and -0.49±2.25 mm Hg for the preserved comparator. These results met the noninferiority limits. Similar results were observed at day 42. There was no difference between groups in the incidence of adverse events or ocular signs. The total ocular symptoms score was better for T2347 than BPLT upon instillation at day 84 (45.9%/44.3%/9.8% of patients with improvement/no change/worsening vs. 33.6%/47.3%/19.1%; P=0.021), reflecting improvements in individual symptoms such as irritation/burning/stinging (P<0.001), and itching (P<0.01) on day 84. Conclusions: Preservative-free latanoprost-timolol fixed combination T2347 showed noninferior efficacy compared with the preserved comparator and was well tolerated

OCTA multilayer and multisector peripapillary microvascular modeling for diagnosing and staging of glaucoma

Purpose: To develop and assess an automatic procedure for classifying and staging glaucomatous vascular damage based on optical coherence tomography angiography (OCTA) imaging. Methods: OCTA scans (Zeiss Cirrus 5000 HD-OCT) from a random eye of 39 healthy subjects and 82 glaucoma patients were used to develop a new classification algorithm based on multilayer and multisector information. The averaged circumpapillary retinal nerve fiber layer (RNFL) thickness was also collected. Three models, support vector machine (SVM), random forest (RF), and gradient boosting (xGB), were developed and optimized for classifying between healthy and glaucoma patients, primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG), and glaucoma severity groups. Results: All the models, the SVM (area under the receiver operating characteristic [AUROC] 0.89 ± 0.06), the RF (AUROC 0.86 ± 0.06), and the xGB (AUROC 0.85 ± 0.07), with 26, 22, and 29 vascular features obtained after feature selection, respectively, presented a similar performance to the RNFL thickness (AUROC 0.85± 0.06) in classifying healthy and glaucoma patients. The superficial vascular plexus was the most informative layer with the infero temporal sector as the most discriminative region of interest. No significant differentiation was obtained in discriminating the POAG from the NTG group. The xGB model, after feature selection, presented the best performance in classifying the severity groups (AUROC 0.76± 0.06), outperforming the RNFL (AUROC 0.67± 0.06). Conclusions: OCTA multilayer and multisector information has similar performance to RNFL for glaucoma diagnosis, but it has an added value for glaucoma severity classification, showing promising results for staging glaucoma progression. Translational Relevance: OCTA, in its current stage, has the potential to be used in clinical practice as a complementary imaging technique in glaucoma management

Conjunctival effects of a selective nasal pollen provocation

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Comparison of a travoprost BAK-free formulation preserved with polyquaternium-1 with BAK-preserved travoprost in ocular hypertension or open-angle glaucoma

Purpose. To demonstrate that the intraocular pressure (IOP)-lowering effect of travoprost 0.004% preserved with polyquaternium-1 (travoprost benzalkonium chloride [BAK]-free) is non-inferior to that of travoprost 0.004% preserved with benzalkonium chloride (travoprost BAK) in patients with ocular hypertension or open-angle glaucoma. Methods. A total of 371 patients randomly received travoprost BAK-free (n=185) or travoprost BAK (n=186) dosed once daily in the evening for 3 months. Patients were evaluated at 9 am, 11 am, and 4 pm at baseline, weeks 2 and 6, and month 3. Intraocular pressure was also evaluated 36 and 60 hours after the month 3 visit. Results. Travoprost BAK-free is non-inferior to travoprost BAK. The 95% upper confidence limits for the difference in mean IOP at month 3 (primary efficacy) were 0.5 mmHg, 0.6 mmHg, and 0.5 mmHg, at 9 am, 11 am, and 4 pm, respectively. Mean IOP reductions from baseline ranged from 7.6 to 8.7 mmHg in the travoprost BAK-free group and from 7.7 to 9.2 mmHg in the travoprost BAK group. At 36 and 60 hours after the last dose, mean IOP remained 6.8 mmHg and 5.7 mmHg below baseline in the travoprost BAK-free group, vs 7.3 mmHg and 6.0 mmHg in the travoprost BAK group, respectively. The safety profile of travoprost BAK-free was similar to that of travoprost BAK. Conclusions. Travoprost BAK-free safely and effectively lowers IOP in eyes with open-angle glaucoma or ocular hypertension. This BAK-free formulation has comparable safety, efficacy, and duration of IOP-lowering effect to travoprost preserved with BAK. Travoprost BAK-free is an effective option for IOP reduction while avoiding BAK exposure.status: publishe

Microvascular damage assessed by optical coherence tomography angiography for glaucoma diagnosis: a systematic review of the most discriminative regions

A growing number of studies have reported a link between vascular damage and glaucoma based on optical coherence tomography angiography (OCTA) imaging. This multitude of studies focused on different regions of interest (ROIs) which offers the possibility to draw conclusions on the most discriminative locations to diagnose glaucoma. The objective of this work was to review and analyse the discriminative capacity of vascular density, retrieved from different ROIs, on differentiating healthy subjects from glaucoma patients. PubMed was used to perform a systematic review on the analysis of glaucomatous vascular damage using OCTA. All studies up to 21 April 2019 were considered. The ROIs were analysed by region (macula, optic disc and peripapillary region), layer (superficial and deep capillary plexus, avascular, whole retina, choriocapillaris and choroid) and sector (according to the Garway–Heath map). The area under receiver operator characteristic curve (AUROC) and the statistical difference (p-value) were used to report the importance of each ROI for diagnosing glaucoma. From 96 screened studies, 43 were eligible for this review. Overall, the peripapillary region showed to be the most discriminative region with the highest mean AUROC (0.80 ± 0.09). An improvement of the AUROC from this region is observed when a sectorial analysis is performed, with the highest AUROCs obtained at the inferior and superior sectors of the superficial capillary plexus in the peripapillary region (0.86 ± 0.03 and 0.87 ± 0.10, respectively). The presented work shows that glaucomatous vascular damage can be assessed using OCTA, and its added value as a complementary feature for glaucoma diagnosis depends on the region of interest. A sectorial analysis of the superficial layer at the peripapillary region is preferable for assessing glaucomatous vascular damage

Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188

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Use of colour Doppler imaging in ocular blood flow research

The main objective of this report is to encourage consistent quality of testing and reporting within and between centres that use colour Doppler imaging (CDI) for assessment of retrobulbar blood flow. The intention of this review is to standardize methods in CDI assessment that are used widely, but not to exclude other approaches or additional tests that individual laboratories may choose or continue to use.status: publishe