Effect of brimonidine on vascular density and imagej-derived flow index of optic nerve head and macula in primary open angle glaucoma.

PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.

Association of Postural Blood Pressure Response With Disease Severity in Primary Open Angle Glaucoma.

PRCIS: Patients with primary open angle glaucoma (POAG) demonstrated exaggerated postural blood pressure dip in recumbency that was positively correlated with the severity of glaucomatous optic neuropathy (GON). Postural dip testing can be used clinically as a marker of systemic vascular dysregulation in GON risk assessment. OBJECTIVE: To investigate whether patients with POAG demonstrated abnormal postural blood pressure response to recumbency and whether such abnormal postural response correlated with GON severity. PATIENTS AND METHODS: This is a prospective observational study where 47 patients with POAG underwent intraocular pressure and systemic arterial blood pressure, systolic blood pressure (SBP) and diastolic blood pressure (DBP), measurement in seated and after 20-minute recumbency positions. Mean arterial blood pressure (MABP) was calculated for seated and recumbent positions. The percentage difference between seated and recumbent SBP, DBP, and MABP was calculated according to which participants were divided into 3 groups, that is, nondippers, normal dippers, and exaggerated dippers with percentage dips of <10%, ≥10%≤20%, >20%, respectively. Participants underwent optical coherence tomography of optic nerve head to measure retinal nerve fiber layer thickness (RNFLT) which was used as a structural biomarker of GON. RESULTS: RNFLT was lower in exaggerated dippers than in nondippers and normal dippers. There was a negative correlation between postural dip and average RNFLT. Linear regression showed that postural dip was associated with lower RNFLT independent of age and intraocular pressure. The χ 2 independence test demonstrated a strong relation among corresponding dip groups for SBP, DBP, and MABP. However, it showed no significant relation between hypertension and postural dip. Fisher exact test showed no relation between antihypertensive medication and postural dip. CONCLUSIONS: Patients with POAG demonstrated abnormal postural blood pressure response comprising exaggerated recumbent dip which was positively correlated with disease severity. Postural dip assessment may serve as a simple clinic-based test of systemic vascular dysregulation as part of GON risk evaluation.

Relative Flow Index as a Novel Optical Coherence Tomography Angiography Biomarker in Primary Open Angle Glaucoma.

PRCIS: Relative flow indices as novel optical coherence tomography angiography (OCTA) biomarkers demonstrated reduced optic nerve head and peripapillary large vessel and capillary perfusion in primary open angle glaucoma (POAG). Large vessel perfusion correlated with disease severity and progression. PURPOSE: To introduce relative flow indices as novel OCTA biomarkers and their pathologic insights in POAG. MATERIALS AND METHODS: This is a retrospective case-control study where 57 POAG and 57 control eyes were included. OCTA 4.5×4.5 mm optic nerve head (ONH) were analyzed using ImageJ 1.53t to calculate global flow indices (GFIs) and relative flow indices (RFIs) for whole image optic nerve head, isolated radial peripapillary capillary plexus, and isolated large vessel angiograms. RESULTS: Retinal nerve fiber layer thickness (RNFLT), ONH vascular density (VD), except inside disc and large vessel VD, GFIs, and RFIs were lower in POAG than control. There was a positive correlation between RNFLT and both VD and GFIs. Among RFIs, only large vessel RFI (ONHLVRFI) demonstrated a positive correlation with average RNFLT. Linear regression demonstrated a significant positive coefficient for ONHLVRFI with RNFLT as the dependent variable. The area under receiver operating characteristic curve showed diagnostic accuracy ranging fair, good, and excellent for all biomarkers. Inferior RNFLT had the highest area under the curve (0.922) while optic nerve head large vessel density had the lowest (0.523). CONCLUSIONS: POAG showed structural loss of RNFL neurovascular unit manifesting as positively correlated reduction of VD and RNFLT. Also, POAG had lower global perfusion of the optic nerve head and peripapillary area, resulting in the positively correlated reduction of GFIs and RNFLT. Although RFIs were lower in POAG, only ONHLVRFI demonstrated a positive correlation and regression with RNFLT, implying that large vessel hypoperfusion was associated with POAG severity and progression.

Validity of a novel optical coherence tomography angiography flow index in a cohort of primary open angle glaucoma.

BACKGROUND: Vascular mechanisms are implicated in many ocular diseases. Therefore, different vascular imaging modalities are used in management of such conditions. Optical coherence tomography angiography (OCTA) has high spatial resolution and segmentable 3D volumetric sampling enabling isolation of retinal and peripapillary vascular beds. However, OCTA only indirectly derives quantitative flow data i.e. velocimetry through methods and algorithms liable to limitations like signal saturation. This study introduces and validates novel mathematical OCTA flow indices that may compensate for some OCTA velocimetric limitations. METHODS: Thirty-seven eyes of 23 POAG patients were included. Each underwent baseline and follow-up assessment one month thereafter. Assessment comprised full ophthalmological examination, intraocular pressure (IOP), systemic arterial blood pressure (SABP) and OCTA macula and ONH. Angiograms were processed using ImageJ to calculate OCTA intensity-based flow indices (FIOs), for superficial vascular plexus (SVP), deep vascular plexus (DVP) and optic nerve head vascular plexus (ONH-RPC), i.e. SFIO, DFIO and ONHFIO respectively. Mean ocular perfusion pressure (MOPP) was calculated using IOP and SABP. OCTA vascular densities (VD) and MOPP were used to calculate three respective mathematical flow indices (FIMs) for SVP, DVP and ONH-RPC, based on Hagen-Poiseuille law, i.e. SFIM, DFIM, ONHFIM respectively. Pearson test was used for correlation between the two sets of indices. Intraclass correlation coefficient (ICC) was tested for baseline and follow-up values for each index. RESULTS: There was positive correlation between the three FIMs and their respective FIOs at baseline and follow-up ranging between high and moderate. Correlation coefficients (CCs) were 0.773 and 0.609 for SFIM and SFIO P-value < 0.001, 0.829 and 0.624 for DFIM and DFIO P-value < 0.001 and 0.516 and 0.737 for ONHFIM P-value = 0.001 for baseline and follow-up respectively. ICCs were 0.772 P-value < 0.001, 0.328 P-value = 0.022 and 0.888 P-value < 0.001 for SFIM, DFIM and ONHFIM respectively. For SFIO, DFIO and ONHFIO, ICCs were 0.420 P-value = 0.004, 0.079 P-value = 0.320 and 0.833 P-value < 0.001 respectively. CONCLUSION: The novel FIMs are reliable alternatives to FIOs and may compensate for OCTA signal saturation in extremes of MOPP. SFIM and ONHFIM showed high ICCs with excellent reliability. While DFIM demonstrated low ICC indicating poor reliability, it still performed better than its corresponding DFIO.

Purtscher-like retinopathy following coronary artery bypass grafting in an antiphospholipid syndrome patient: a case report.

BACKGROUND: Purtscher retinopathy is a rare occlusive microangiopathy comprising a constellation of retinal signs including cotton wool spots, retinal hemorrhages and Purtscher flecken. While classical Purtscher must be antedated by a traumatic incident, Purtscher-like retinopathy is used to refer to the same clinical syndrome in the absence of trauma. Various non-traumatic conditions have been associated with Purtscher-like retinopathy e.g. acute pancreatitis, preeclampsia, parturition, renal failure and multiple connective tissue disorders. In this case study, we report the occurrence of Purtscher-like retinopathy following coronary artery bypass grafting in a female patient with primary antiphospholipid syndrome (APS). CASE PRESENTATION: A 48-year-old Caucasian female patient presented with a complaint of acute painless diminution of vision in the left eye (OS) that occurred approximately two months earlier. Clinical history revealed that the patient underwent coronary artery bypass grafting (CABG) two months earlier and that visual symptoms started 4 days thereafter. Furthermore, the patient reported undergoing percutaneous coronary intervention (PCI) one year before for another myocardial ischemic event. Ophthalmological examination revealed multiple yellowish-white superficial retinal lesions i.e. cotton-wool spots, exclusively in the posterior pole and predominantly macular within the temporal vascular arcades only OS. Fundus examination of the right eye (OD) was normal and the anterior segment examination of both eyes (OU) was unremarkable. A diagnosis of Purtscher-like retinopathy was made based on clinical signs, suggestive history and consolidated by fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) of macula, optic nerve head (ONH) according to the diagnostic guidelines of Miguel. The patient was referred to a rheumatologist to identify the underlying systemic cause and was diagnosed with primary antiphospholipid syndrome (APS). CONCLUSIONS: We report a case of Purtscher-like retinopathy complicating primary antiphospholipid syndrome (APS) following coronary artery bypass grafting. This conveys a message to clinicians that patients presenting with Purtscher-like retinopathy should undergo meticulous systemic work-up in order to identify potentially life-threatening underlying systemic diseases.

Early onset monocular hydroxychloroquine maculopathy in a systemic lupus erythematosus patient with history of central retinal artery occlusion: a case report.

BACKGROUND: Hydroxychloroquine is a widely used medication for various clinical conditions mainly rheumatological and dermatological autoimmune diseases e.g. systemic lupus erythematosus, rheumatoid arthritis and psoriasis. While it is considered a safe medication, it is well-established that it can cause retinal toxicity i.e. HCQ maculopathy. Guidelines for HCQ retinal toxicity screening include factors like body weight, daily dose, duration, systemic diseases and retinal diseases. In this case study, we report a specific association between CRAO as a retinal disease and early onset HCQ maculopathy in a SLE patient. CASE PRESENTATION: A 42-year-old Caucasian female SLE patient presented with a complaint of gradual progressive painless diminution of vision in the left eye that started 16 months earlier. Clinical evaluation of the patient revealed a history of sudden profound painless diminution of vision in the same eye 18 months earlier after which the patient experienced only partial improvement of vision. That episode of sudden diminution of vision was attributed to left CRAO, complicating SLE-related thrombophilia, confirmed by fundus fluorescein angiography. Based on that diagnosis, the patient had been prescribed HCQ. At the time of presentation, fundus examination revealed left bull's eye maculopathy and right normal fundus. Therefore, a diagnosis of HCQ maculopathy in the left eye was made after exclusion of other causes of unilateral bull's eye maculopathy. CONCLUSION: Our case study is the first to report an association between CRAO as a specific retinal disease and early onset of HCQ maculopathy in a SLE patient. The unilateral bull's eye presentation which occurred in the eye with CRAO after only 16 months of HCQ treatment highly suggests that CRAO is probably the cause of such unusually early maculopathy. This case report highlights the importance of retinal diseases as risk factors for HCQ maculopathy. It also points out the lack of specific evidence concerning the association between specific retinal diseases and HCQ maculopathy.

Macular and Optic Nerve Microvascular Alteration in Relation to Axial Length, by Optical Coherence Tomography Angiography (OCTA).

Aim: To study the effect of axial length (AL) on quantitative characterization of macular and optic nerve microvasculature using optical coherence tomography angiography (OCTA) in healthy individuals. Methods: A cross-sectional study where participants were divided into 3 groups according to AL; A: ≤22.5 mm, B: 22.6-24.5 mm, C: >24.5 mm. Superficial vascular density (SVD), deep vascular density (DVD), foveal avascular zone (FAZ), and radial peripapillary capillary density (RPCD) were calculated using OCTA. Pearson correlation was run to identify the relation between AL and study parameters. Results: One hundred and twelve eyes of 56 participants (20 males, 36 females) were included. Mean FAZ was 0.33 ± 0.15 mm2, 0.27 ± 0.1 mm2 and 0.28 ± 0.2 mm2 in Groups A, B, and C, respectively (p value 0.073). No significant difference was found between 3 groups, as regards superficial foveal density and vessel density inside the disc. Deep foveal density was significantly lower in Group A in comparison to Groups B and C (p value 0.021 and 0.005, respectively). As for other parameters of SVD, DVD and RPCD, no significant difference was observed between Groups A and B; however, the same parameters were significantly lower in Group C when compared to Group A and B. AL was found to be negatively correlated to FAZ (r -0.191, p value 0.043) and most of parameters of SVD, DVD, and RPCD (p value < 0.0001). Conclusion: Most of optic nerve and macular microvascular parameters were significantly lower in eyes with longer axial lengths when compared to those with shorter axial lengths. Moreover, most of these parameters were negatively correlated with AL.

Horizontal Extraocular Muscle Insertion Site in Relation to Axial Length Using Swept-Source Anterior Segment OCT.

PURPOSE: The purpose of this study was to correlate between the axial length of the globe and the insertion site of horizontal extraocular muscles using swept-source anterior segment optical coherence tomography (SS-ASOCT), with posing an equation to calculate the muscle insertion site from the axial length. METHODS: The study design was observational and cross-sectional. It was performed on 157 eyes of 157 healthy subjects. The distance of the medial rectus (MR) and the lateral rectus (LR) insertion sites from the limbus were measured using SS-ASOCT. The insertion sites' distances were correlated to the axial length (hypermetropes < 22.5 mm, myopes > 24.5). Correlation between numerical variables was done by Pearson's correlation coefficient and confirmed by linear regression analysis and scatter diagrams. RESULTS: The mean MR insertion site was 5.47 ± 0.19 mm in hypermetropes versus 5.68 ± 0.23 mm in myopes, whereas the mean LR insertion site was 6.81± 0.23 mm in hyperopes versus 7.08 ± 0.16 mm in myopes. The axial length showed a moderate positive, but significant, correlation to the insertional position for the medial and lateral rectus muscles (MR: r=0.417, p<0.001; LR: r=0.410, p<0.001). CONCLUSION: Comparing the horizontal extraocular muscle insertion site to axial length using SS-ASOCT showed a significant positive correlation. The model equation for MR insertion: MR (mm) = 4.522 + 0.045 (AXL in mm) with an R = 0.437, R2= 0.191, F=12.071, P<0.001. The model equation for LR insertion: LR (mm) = 5.72 + 0.048 (AXL in mm) with an R = 0.438, R2= 0.192, F=12.116, P<0.001.

Pattern of Intermediate Uveitis in an Egyptian Cohort.

Purpose: To describe the clinical experience with intermediate uveitis at six Egyptian tertiary eye centers.Methods: A multicenter retrospective chart review of all patients with intermediate uveitis seen at six ocular inflammation referral clinics in Egypt between January 2010 and January 2017.Results: The study included a total of 781 patients with intermediate uveitis. The study cohort comprised of 282 male and 499 female patients. In over half of our cohort (58.77%), no specific cause could be confirmed. The remaining patients had sarcoidosis (16.26%), tuberculosis (14.85%), multiple sclerosis (9.09%), and TINU (1.02%). By the end of our study, 62% of the affected eyes had a BCVA better than 20/40Conclusion: More than 40% of our patients with intermediate uveitis had sarcoidosis, tuberculosis, multiple sclerosis, or TINU as the underlying etiology. Owing to their potential morbidity, these diseases need to be considered in Egyptian patients presenting with intermediate uveitis.