Total venous nature of retinal deep capillary plexus inferred by continuity of prominent middle limiting membrane sign in optical coherence tomography.

This study aimed to theoretically identify the vascular nature of the deep capillary plexus (DCP) by examining patients presenting with both paracentral acute middle maculopathy (PAMM) and prominent middle limiting membrane (p-MLM) sign and p-MLM sign alone in spectral-domain optical coherence tomography (SD-OCT). A retrospective review of the medical records of patients with retinal vein or artery occlusion from two tertiary medical centers was performed. Consecutive patients with a clinical diagnosis of all categories of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) (branch or central and ischemic or non-ischemic) who had undergone SD-OCT imaging from January 2015 to May 2020 were recruited and their p-MLM signs and PAMM lesions were assessed. We included 118 patients who presented with p-MLM sign with or without PAMM lesions. Amon them, 40 were female and 78 were male, with a mean age of 61.1 years. Of the 109 patients with both p-MLM sign and PAMM lesions, 23 had branch RAO, two had branch RVO, 67 had central RAO, 13 had central RVO, and four had a combination of central RAO and central RVO. All nine patients with the p-MLM sign alone had central RVO accompanied by cystoid macular edema. In all the enrolled patients, the hyperreflective lines of the p-MLM sign were continuous, regardless of the type of PAMM lesions. In conclusion, when PAMM and p-MLM sign are examined together, further proof regarding the possible complete venous nature of the vasculature of the retinal DCP might be speculated.

Quantitative measures of vortex veins in the posterior pole in eyes with pachychoroid spectrum diseases.

Pachychoroid spectrum diseases have attracted increasing attention, though their pathophysiology has yet to be fully elucidated. In this study, we assessed the vascular diameters of vortex veins in pachychoroid spectrum diseases such as central serous chorioretinopathy (CSC), pachychoroid neovasculopathy without polypoidal lesions (PNV), and pachychoroid neovasculopathy with polypoidal lesions (polypoidal choroidal vasculopathy: PCV). In a retrospective case series of 94 eyes with CSC, 60 eyes with PNV and 57 with PCV, we binarized en face optical coherence tomography (OCT) images of choroidal vortex veins and analyzed the mean diameter of vortex veins. The presence of anastomosis between the superior and inferior vortex veins and central choroidal thickness (CCT) were also evaluated using OCT images. CSC showed significantly larger mean diameter of vortex veins than PCV (P < 0.05). Anastomosis between superior and inferior vortex veins was observed in over 90% of eyes with each pachychoroid spectrum disease. The patients with CSC were the youngest, followed by PNV patients, and then patients with PCV. The largest CCT values were observed in CSC eyes, followed by PNV eyes, and then PCV eyes. CCT correlated with the mean diameter of vortex veins (rs = 0.51, P < 0.01). These findings suggest that congestion of vortex veins might show gradual amelioration corresponding to the development of anastomosis between the superior and inferior vortex veins during the course of progression of pachychoroid spectrum diseases. Moreover, the mean diameter of vortex veins can be used as a parameter indicating choroidal congestion.

Vortex Vein Anastomosis at the Watershed in Pachychoroid Spectrum Diseases.

PURPOSE: To evaluate the vascular changes in vortex veins at the posterior pole in pachychoroid spectrum diseases, including central serous chorioretinopathy (CSC), pachychoroid neovasculopathy without polypoidal lesions (PNV), and pachychoroid neovasculopathy with polypoidal lesions (polypoidal choroidal vasculopathy [PCV]). DESIGN: Retrospective case-control study. PARTICIPANTS: Ninety-two eyes of 89 patients with CSC, 61 eyes of 59 patients with PNV, 63 eyes of 61 patients with PCV, and 25 healthy control eyes of 25 age- and gender-matched participants for each pachychoroid spectrum disease. METHODS: Clinical records of patients with pachychoroid spectrum diseases and healthy controls were reviewed. Multimodal images of each group were analyzed. Swept-source OCT was performed to obtain B-mode and en face images in patients with pachychoroid spectrum diseases and healthy controls. All patients underwent fluorescein angiography, indocyanine green angiography, and OCT. MAIN OUTCOME MEASURES: Vortex vein anastomosis at the watershed, determined using en face OCT, and central choroidal thickness (CCT), measured using B-mode OCT, were examined in patients and healthy controls. Patient ages also were taken into consideration. RESULTS: Patients with CSC were the youngest, followed by patients with PNV, and then those with PCV (P < 0.01, CSC vs. PNV and PNV vs. PCV), whereas CSC eyes showed the highest CCT values, followed by the PNV and then the PCV eyes (P < 0.01, CSC vs. PNV; P < 0.05, PNV vs. PCV). Central choroidal thickness was significantly greater in pachychoroid spectrum diseases than in healthy controls. No significant CCT differences were found among healthy controls. Anastomosis between superior and inferior vortex veins was observed in more than 90% of eyes with pachychoroid spectrum diseases, making this finding significantly more frequent than in healthy controls (P < 0.01, each pachychoroid spectrum disease vs. control). Polypoidal choroidal vasculopathy showed a significantly higher rate of anastomosis than CSC (P < 0.05). CONCLUSIONS: Anastomosis between superior and inferior vortex veins was found to be a common feature in pachychoroid spectrum diseases. Longstanding vortex vein congestion may lead to the development of pachychoroid spectrum diseases. Choroidal congestion may be compensated for by new drainage routes formed via vortex vein anastomosis.

Prognostic Value of Hyperreflective Material on Visual Acuity in Treatment-Naïve BRVO.

BACKGROUND AND OBJECTIVE: To correlate between hyperreflective material (HRM) seen on optical coherence tomography (OCT) and visual outcomes in treatment-naïve acute branch retinal vein occlusion (BRVO). PATIENTS AND METHODS: Demographic and OCT features of patients with acute BRVO were analyzed retrospectively. OCT parameters noted were macular edema type, HRM presence and location, and outer retinal layer integrity. Eyes were separated into two groups: Group 1 (BRVO without HRM) and Group 2 (BRVO with HRM). RESULTS: Forty-seven eyes (67%) were included in Group 1 and 23 eyes (33%) were included in Group 2. Mean presenting logMAR visual acuity in Groups 1 and 2 was 0.521 ± 0.428 (mean Snellen equivalent = 20/66) and 0.627 ± 0.427 (mean Snellen equivalent = 20/85), respectively. Poor vision at final visit was noted in the BRVO with HRM group (P = .027). More intravitreal injections were required for macular edema resolution in the HRM group (4.83 vs. 2.67). CONCLUSIONS: Presence of HRM in BRVO is associated with poorer vision. It can be a useful prognostic biomarker. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:320-327.].

Detection of Occult Arteriovenous Malformation With Annular Array Ultrasonography.

Retinal vascular tortuosity may occur in a wide range of ocular disorders. When retinal vascular tortuosity involves both arteries and veins, and presents unilaterally and without hemorrhage, a diagnosis of Wyburn Mason syndrome (WMS) should be considered due to the potential morbidity and mortality associated with cerebral involvement. Magnetic resonance imaging (MRI) and MRI angiography (MRA) are important tools for identifying cerebral arteriovenous malformations (AVMs), but these imaging modalities have limited spatial resolution to detect very small vascular lesions. Annular array contact ocular ultrasound is a new imaging modality capable of detecting small intraorbital AVMs. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:239-243.].

Retinal Nonperfusion Relationship to Arteries or Veins Observed on Widefield Optical Coherence Tomography Angiography in Diabetic Retinopathy.

Purpose: To evaluate whether retinal capillary nonperfusion is found predominantly adjacent to arteries or veins in eyes with diabetic retinopathy (DR). Methods: Sixty-three eyes from 44 patients with proliferative DR (PDR) or non-PDR (NPDR) were included. Images (12 × 12-mm) foveal-centered optical coherence tomography (OCT) angiography (OCTA) images were taken using the Zeiss Plex Elite 9000. In 37 eyes, widefield montages with five fixation points were also obtained. A semiautomatic algorithm that detects nonperfusion in full-retina OCT slabs was developed, and the percentages of capillary nonperfusion within the total image area were calculated. Retinal arteries and veins were manually traced. Based on the shortest distance, nonperfusion pixels were labeled as either arterial-side or venous-side. Arterial-adjacent and venous-adjacent nonperfusion and the A/V ratio (arterial-adjacent nonperfusion divided by venous-adjacent nonperfusion) were quantified. Results: Twenty-two eyes with moderate NPDR, 16 eyes with severe NPDR, and 25 eyes with PDR were scanned. Total nonperfusion area in PDR (median: 8.93%) was greater than in moderate NPDR (3.49%, P < 0.01). Arterial-adjacent nonperfusion was greater than venous-adjacent nonperfusion for all stages of DR (P < 0.001). The median A/V ratios were 1.93 in moderate NPDR, 1.84 in severe NPDR, and 1.78 in PDR. The A/V ratio was negatively correlated with the total nonperfusion area (r = -0.600, P < 0.0001). The results from the widefield montages showed similar patterns. Conclusions: OCTA images with arteries and veins traced allowed us to estimate the nonperfusion distribution. In DR, smaller nonperfusion tends to be arterial-adjacent, while larger nonperfusion tends toward veins.

Corkscrew retinal vessels and retinal arterial macroaneurysm in a patient with neurofibromatosis type 1: A case report.

RATIONALE: Neurofibromatosis type I (NF-1) is a multisystem autosomal dominant disease characterized by pigmentation and the growth of tumors along nerves in the skin, brain, and other parts of the body. It is caused by a mutation in the NF-1 tumor suppressor gene. NF-1 vascular disease is an important complication of the disease. PATIENT CONCERNS: The study reports a unique case of a patient with NF-1 with 2 simultaneous vascular abnormalities, involving tiny spiral venous changes (corkscrew retinal vessels) and retinal arterial macroaneurysms. Our patient was diagnosed with NF-1 as she met the following National Institutes of Health consensus criteria for the diagnosis of NF-1: more than 6 cafe au lait macules, of a maximum diameter ≥15mm, 2 neurofibromas within the dermis, and Lisch nodules on the iris. DIAGNOSES: Retinal arterial macroaneurysm in the left eye, corkscrew retinal vessels related to NF-1 and Neurofibromatosis type I. INTERVENTIONS: Due to the possibility of automatic involution of macroaneurysms, recovery may not affect vision (4). A cardiologist advised the patient to take nifedipine tablets (30mg/d) to treat her high blood pressure while continuing observation of the macroaneurysms. OUTCOMES: Preretinal, intraretinal, and subretinal hemorrhage near the retinal artery aneurysm in the patient showed partial absorption at 3 months of follow-up. LESSONS: Our analysis suggests that retinal macroaneurysm formed in the patient's body are due to neurofibroma type I secondary hypertension. The case study also indicated the symptoms of newly discovered neurofibroma type I which led to retinal microvascular abnormalities. We believe that such changes in eye blood vessels are rare and this case provides an insight to the field of neurology and ophthalmology.

Comparison of ranibizumab versus dexamethasone for macular oedema following retinal vein occlusion: 1-year results of the COMRADE extension study.

PURPOSE: The COMRADE studies are the first randomized controlled head-to-head trials comparing the efficacy and safety of intravitreal ranibizumab versus dexamethasone (DEX) in patients with macular oedema secondary to retinal vein occlusion (RVO). The COMRADE extension trial was designed to provide additional 6-month data of patients who completed the core studies. METHODS: In this open-label, phase IV study patients who completed the COMRADE core studies were prospectively enrolled. Overall, 92 branch RVO (BRVO) patients (ranibizumab 52, DEX 40) and 83 central RVO (CRVO) patients (ranibizumab 61, DEX 22) were treated, and 94.6% of BRVO patients and 97.6% of CRVO patients completed the extension study. Patients were assigned to the same treatment group as in the core studies. Patients were monitored monthly and received either 0.5 mg ranibizumab or a 0.7 mg DEX implant as needed. RESULTS: Over the course of the extension, treatment-emergent adverse events (TEAEs) of the study eye occurred in 55.8% of BRVO patients on ranibizumab and in 62.5% of those on DEX. Among CRVO patients, 65.5% in the ranibizumab group and 59.1% in the DEX group developed TEAEs. Overall, elevated intraocular pressure (IOP) was more frequent with DEX than ranibizumab treatment. Mean average change in best-corrected visual acuity (BCVA) in BRVO patients was significantly better for ranibizumab than DEX (p = 0.0249). The CRVO results were consistent with BRVO's, although not significant (p = 0.1119). CONCLUSION: When used according to the European labels, ranibizumab revealed a better ocular safety profile and produced greater average BCVA gains than DEX. By the end of the additional 6-month study period, this difference in BCVA was more pronounced in BRVO as in CRVO patients. The main limitation of the COMRADE studies was that DEX patients received only a single intravitreal treatment during the first 6 months, which is presumably not adequate. However, frequent DEX implants could lead to more steroid-related side effects, especially to an increased intraocular pressure.

In Vivo Imaging of Retinal Hypoxia Using HYPOX-4-Dependent Fluorescence in a Mouse Model of Laser-Induced Retinal Vein Occlusion (RVO).

Purpose: To demonstrate the utility of a novel in vivo molecular imaging probe, HYPOX-4, to detect and image retinal hypoxia in real time, in a mouse model of retinal vein occlusion (RVO). Methods: Retinal vein occlusion was achieved in adult mice by photodynamic retinal vein thrombosis (PRVT). One or two major retinal vein(s) was/were occluded in close proximity to the optic nerve head (ONH). In vivo imaging of retinal hypoxia was performed using, HYPOX-4, an imaging probe developed by our laboratory. Pimonidazole-adduct immunostaining was performed and used as a standard ex vivo method for the detection of retinal hypoxia in this mouse RVO model. The retinal vasculature was imaged using fluorescein angiography (FA) and isolectin B4 staining. Retinal thickness was assessed by spectral-domain optical coherence tomography (SD-OCT) analysis. Results: By application of the standard ex vivo pimonidazole-adduct immunostaining technique, retinal hypoxia was observed within 2 hours post-PRVT. The observed hypoxic retinal areas depended on whether one or two retinal vein(s) was/were occluded. Similar areas of hypoxia were imaged in vivo using HYPOX-4. Using OCT, retinal edema was observed immediately post-PRVT induction, resolving 8 days later. Nominal preretinal neovascularization was observed at 10 to 14 days post-RVO. Conclusions: HYPOX-4 is an efficient probe capable of imaging retinal hypoxia in vivo, in RVO mice. Future studies will focus on its use in correlating retinal hypoxia to the onset and progression of ischemic vasculopathies.

[Selective symptomatic therapy of macular edema due to occlusive processes in retinal venous system]. / . Simptomaticheskaia selektivnaia terapiia makuliarnogo oteka pri okkliuzionnykh protsessakh v sisteme retinal'nykh ven.

AIM: to evaluate the effect of dexamethasone intravitreal implant on the functional state of the eye in macular edema associated with central retinal vein occlusion. MATERIAL AND METHODS: The study included two groups of patients: group 1 (control group) - 8 patients (16 eyes) without ocular pathology and group 2 (study group) - 8 patients (8 eyes) with macular edema on the background of newly diagnosed thrombosis of the central retinal vein. All the patients from the study group underwent insertion of an intravitreal dexamethasone implant - Ozurdex. Best corrected visual acuity (BCVA) and retinal light sensitivity of the central visual field were followed up. The maximum follow-up period was 12 months. RESULTS: In group 1 (controls), BCVA averaged 0.93±0.2 and retinal light sensitivity of the central visual field - 19.01±1.18 dB. In group 2, baseline BCVA and retinal light sensitivity were 0.08±0.02 and 4.23±0.2 dB, 1 month after Ozurdex implantation - 0.21±0.04 and 11.77±0.98 dB, at 12 months - 0.23±0.17 and 5.2±0.78 dB, respectively. CONCLUSION: Macular edema associated with central retinal vein thrombosis has a strong deteriorating effect on the functional state of the eye. The dexamethasone intravitreal implant in patients with postthrombotic macular edema contributes to functional improvement, including BCVA and light sensitivity of the central retina, over the first year. At that, different functional parameters show different dynamics after dexamethasone treatment. Light sensitivity values, in contrast to BCVA, change unevenly and significantly during the year. Intravitreal implantation of a dexamethasone implant in patients with postthrombotic macular edema is an effective symptomatic treatment of occlusive processes within the retinal venous system.

Significant Correlation between Retinal Venous Tortuosity and Aqueous Vascular Endothelial Growth Factor Concentration in Eyes with Central Retinal Vein Occlusion.

PURPOSE: To determine whether the degree of venous tortuosity is significantly correlated with the aqueous vascular endothelial growth factor (VEGF) concentration in eyes with a central retinal vein occlusion (CRVO). METHODS: We reviewed the medical records of 32 eyes of 32 patients who had macular edema due to a CRVO. All of the patients were examined at the Nagoya University Hospital and were scheduled to receive an intravitreal injection of bevacizumab (IVB) or ranibizumab (IVR) within 12 weeks of the onset of the CRVO to treat the macular edema. Aqueous humor was collected just before the IVB or IVR, and the VEGF concentration was determined by enzyme-linked immunosorbent assay (ELISA). The venous tortuosity index was calculated by dividing the length of the retinal veins by the chord length of the same segment. The correlation between the mean tortuosity index of the inferotemporal and supratemporal branches of the retinal vein and the aqueous VEGF concentration was determined. RESULTS: The mean aqueous VEGF concentration was 384 ± 312 pg/ml with a range of 90 to 1077 pg/ml. The degree of venous tortuosity was significantly correlated with the VEGF concentration in the aqueous. (r = 0.49, P = 0.004), with the foveal thickness (r = 0.40, P = 0.02), and with the best-corrected visual acuity (r = 0.38, P = 0.03). CONCLUSIONS: The significant correlation between the aqueous VEGF concentration and the venous tortuosity indicates that the degree of retinal venous tortuosity can be used to identify eyes that are at a high risk of developing neovascularization.