Quantitative Assessment of Lid Margin Vascularity Using Swept-Source Optical Coherence Tomography Angiography.

Purpose: To evaluate the ability of swept-source optical coherence tomography angiography (SS-OCTA) to assess lid margin vascularity. Methods: This prospective, cross-sectional trial enrolled 125 participants, including 15 control subjects and 110 meibomian gland dysfunction (MGD) patients. Lid margin blood flow density (LMBFD) was obtained using SS-OCTA. LMBFD was assessed for repeatability in 54 of 125 participants and for reproducibility in 23 of 125 participants. The efficacy of LMBFD was validated in the 125 participants, who were divided into mild (n = 46), moderate (n = 42), and severe groups (n = 37) according to the lid margin vascularity severity shown in the slit-lamp photographs. Correlations between LMBFD and MG-related parameters, such as ocular surface disease index (OSDI), fluorescein tear break-up time (FTBUT), cornea fluorescein staining (CFS), lid margin score (LMS), and meibomian gland expressibility (ME), were analyzed in all 125 participants. Results: Repeatability and reproducibility coefficients were satisfactorily high in the scan mode with a scan area of 6 mm × 6 mm (intraclass correlation coefficient [ICC] repeatability = 0.905; ICC reproducibility = 0.986) and a scan area of 9 mm × 9 mm (ICC repeatability = 0.888; ICC reproducibility = 0.988). The LMBFD gradually increased in the mild, moderate, and severe groups (P < 0.001). LMBFD was significant correlated with OSDI (r = 0.290, P = 0.001), FTBUT (r = -0.195, P = 0.030), CFS (r = 0.352, P < 0.001), ME (r = 0.191, P = 0.033), and LMS (r = 0.370, P < 0.001). Conclusions: LMBFD may be a noninvasive, repeatable, reproducible, and efficient index for the quantitative evaluation of eyelid margin vascularity in the future. Translational Relevance: We demonstrated that SS-OCTA has the potential to evaluate the eyelid margin vascularity in MGD patients and guide future treatment strategies in clinics.

[Laser Doppler flowmetry in the diagnosis of chronic mixed blepharitis]. / Lazernaya dopplerovskaya floumetriya v diagnostike khronicheskogo smeshannogo blefarita.

Chronic mixed blepharitis accounts for 51.7% of all ophthalmic diseases. The use of laser Doppler flowmetry (LDF) in the diagnosis of this disease can help establish the initial manifestations of the inflammatory process in the eyelids, which is important for the prevention of possible complications - dry eye disease. PURPOSE: This study was conducted to determine the sensitivity and specificity of the LDF method in the diagnosis of chronic mixed blepharitis based on the study of microcirculatory changes in the eyelid skin. MATERIAL AND METHODS: The study included 23 patients with chronic mixed blepharitis (mean age 67±5.8 years) and 18 healthy volunteers (mean age 63±1.1 years). LDF was performed using the LAZMA MC-1 device. ROC analysis was used to determine sensitivity and specificity. RESULTS: A typical disturbance of the eyelid skin microcirculation was revealed in chronic mixed blepharitis - ischemia - with inhibition of the intensity of the functioning of blood flow regulatory systems and moderate activation of the lymph flow. The sensitivity and specificity of the coefficient of variation (reflecting the vasomotor activity of microvessels) of blood flow was 71.43 and 71.43%, lymph flow - 65.71 and 80.00%; myogenic rhythms of blood flow - 83.33 and 85.71%, lymph flow - 66.67 and 71.43%; neurogenic rhythms of blood flow - 75.00 and 78.57%, lymph flow - 91.67 and 78.57%, respectively. CONCLUSION: Laser Doppler flowmetry of the eyelid skin in combination with clinical, functional and instrumental research methods helped reveal with high sensitivity and specificity the eyelid damage in chronic mixed blepharitis. This method allows assessment of the condition of the eyelids in individuals without diseases of the anterior segment of the eye.

Clinical Relevance of the Variability of the Infraorbital Arterial Anatomy Evaluated by Three-Dimensional Computed Tomography.

BACKGROUND: Knowledge of the anatomy of the infraorbital artery (IOA) is crucial for the rejuvenation of the anterior medial aspect of the midface; however, studies adequately describing the anatomy of the IOA branches are lacking, and their connection with the ophthalmic artery branches remains unclear. OBJECTIVES: This study aims to elucidate the anatomical characteristics of the IOA in its deployment within the lower eyelid using three-dimensional (3D) technology, thereby offering an anatomical foundation for clinical surgical procedures. METHODS: An analysis was conducted on computed tomography scans of 132 cadaveric head sides post-contrast injection, utilizing the Mimics software for reconstruction. The study focused on examining the anastomosis of the IOA, its principal branches, and the branches emanating from the ophthalmic artery. RESULTS: The prevalence of type I IOA was observed at 38.6% (51/132), while Type II IOA was found in 61.4% (81/132) of cases. A 7.6% incidence (10/132) of IOA directly anastomosing with the angular artery was noted. The presence of palpebral branches (PIOA) was identified in 57.6% (76/132) of instances. In the lower eyelid, four distinct distribution patterns of IOA were discerned: The likelihood of Type I PIOA was 5.3%, whereas for Types IIA, IIB, and IIC PIOA, the probabilities were 8.3%, 32.6%, and 11.4%, respectively. The occurrence of the orbital branch of IOA was recorded at 41.7% (55/132). CONCLUSIONS: 3D technology can map IOA variants and identify the deployment patterns of IOA branches in the lower eyelid vascular vesicles at high resolution as a guide in clinical practice. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Origin and Course of the Blood Supply to the Lower Eyelid Orbital Fat: Anatomical Study and Clinical Significance.

PURPOSE: The aim of this study is to investigate the origin and course of the orbital fat arterial supply in the lower eyelid using traditional anatomy and three-dimensional computed tomography (CT). METHODS: Twenty-seven cadaver heads were infused with mercury sulfide contrast media through the ophthalmic artery, maxillary artery, transverse facial artery, and facial artery. CT images were obtained after contrast agent injection, three-dimensional CT scans were reconstructed, and the cadaver heads were dissected. RESULTS: Forty-five qualified hemifaces showed that the orbital fat arterial supply in the lower eyelid originates primarily from the inferomedial muscular trunk (IMT) of the ophthalmic artery and the orbital branch of the infraorbital artery. The medial branch of the IMT terminated at the medial fat pad (35.6%) or the orbital floor (64.4%). The lateral branch terminated at the inferior oblique (IO) muscle (28.9%) or the central and lateral fat pads (17.8%). In 53.3%, the lateral branch extended to the anterior part of the lateral fat pad and terminated in the orbital wall or the zygomaticoorbital foramina. The orbital branch of the infraorbital artery coursed between the orbital floor and the orbital fat, providing supply to the IO muscle, inferior rectus (IR) muscle, nasolacrimal duct, and orbital fat. CONCLUSION: This study elucidated the origin and course of the orbital fat arterial supply in the lower eyelid, which may help to avoid reducing the blood supply of the orbital fat pedicles during surgery. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Bilateral Traumatic Carotid-Cavernous Fistula in a Child: Corkscrew Eyelid Vessels as an Indicator of Severe Congestion.

An 11-year-old girl presented with bilateral traumatic caroticocavernous fistula associated with corkscrew eyelid vessels, which were considered indicators of severe congestive disease in this case. Coil embolization was performed; similar to other congestive findings such as proptosis, orbital bruit, increased intraocular pressure, congested scleral and retinal vessels, engorged eyelid vessels resolved immediately after coil embolization. This pediatric case is unique given the caroticocavernous fistula was bilateral and was associated with prominent dilatation of the eyelid vessels, named for the first time as corkscrew eyelid vessels.

A case series: 3-dimensional computed tomographic study of the superior orbital vessels: Superior orbital arcades and their relationships with the supratrochlear artery and supraorbital artery.

BACKGROUND: Vascular complications from periorbital intravascular filler injection are major safety concerns. OBJECTIVE: To thoroughly describe the superior orbital vessels near the orbital rim and propose considerations for upper eyelid and forehead injections. METHODS: Fifty-one cadaver heads were infused with lead oxide contrast media through the external carotid artery, internal carotid artery, and facial and superficial temporal arteries. Computed tomography (CT) images were obtained after contrast agent injection, and 3-dimensional CT scans were reconstructed by using a validated algorithm. RESULTS: Eighty-six qualified hemifaces clearly showed the origin, depth, and anastomoses of the superior orbital vessels, which consistently deployed 2 distinctive layers: deep and superficial. Of all hemifaces, 59.3% had deep superior orbital vessels near the orbital rim, including 44.2% with deep superior orbital arcades and 15.1% with deep superior orbital arteries, which originated from the ophthalmic artery. Additionally, 97.7% of the hemifaces had superficial superior orbital arcades, for which 4 origins were identified: ophthalmic artery, superior medial palpebral artery, angular artery, and anastomosis between the angular and ophthalmic arteries. LIMITATIONS: The arterial depth estimated from 3-dimensional CT needs to be confirmed by standard cadaver dissection. CONCLUSION: This study elucidated novel arterial systems and proposed considerations for upper eyelid and forehead injections.

Anatomical and ultrasound-based injections for sunken upper eyelid correction.

BACKGROUND: A needle or a cannula can be safely used during filler injection procedures to correct a sunken upper eyelid. To date, there are no precise injection points recommended that are based on an anatomical study. OBJECTIVE: This study systematically investigated the vascular pattern and depth of forehead arteries at the periorbital area of upper eyelid. METHODS: Twenty cadavers were dissected in this study. Additional data were obtained from 30 healthy volunteers using Doppler ultrasound imaging with high-frequency probe. RESULTS: The ophthalmic artery divided into two opposite primary branches: the superior and inferior orbitoglabellar arteries running along the orbital rim. After the supratrochlear artery arose from the superior orbitoglabellar artery at the medial eyebrow, the supraorbital artery either divided from this artery near the supraorbital foramen or emerged as an individual artery from the supraorbital notch. The inferior orbitoglabellar artery gave off the radix artery superior to the medial canthal tendon. The radix artery divided into two opposite branches: the dorsal nasal artery going to the nose and the paracentral artery going to the glabella. Ultrasound imaging revealed a subcorrugator space that a cannula can safely pass through. At the supraorbital foramen/notch, the supraorbital artery traveled very close to the bone. Based on the anatomical data collected, the following injection points for a needle and a cannula technique are recommended. CONCLUSION: Correction of a sunken upper eyelid is a dangerous procedure which should be performed only by experienced physicians. However, with precise anatomical knowledge and correct techniques, optimal outcomes can be safely achieved.

Botulinum Toxin Type A Attenuates Apoptosis in Human Dermal Microvascular Endothelial Cells Exposed to an In Vitro Model of Ischemia/Reperfusion Injury.

BACKGROUND: Botulinum toxin type A (BTXA) has been reported to increase survival of critically ischemic skin flaps; however, the effect of BTXA in human dermal microvascular endothelial cells (HDMECs) remains to be investigated. This study aimed to investigate the protective effect of BTXA in HDMECs exposed to an in vitro model of ischemia/reperfusion injury. METHODS: HDMECs were isolated from human upper eyelid tissue and were randomly divided into 3 groups: 1. CONTROL GROUP: culture under normoxic conditions (95% air and 5% CO2); 2. hypoxia/reoxygenation (H/R) group: culture in a hypoxic incubator (94% N2 + 5% CO2 + 5% O2) for 8 hours, followed by culture in saturated aerobic culture medium for 24 hours; and 3. BTXA group: treatment with BTXA for 12 hours before exposure to hypoxic conditions. Flow cytometry was used to analyze the apoptosis of HDMECs, and western blotting was used to detect the expression of apoptosis-related proteins. RESULTS: H/R leads to severe injury in HDMECs, as evidenced by an increase in the percentage of apoptosis and an increase in expression of apoptosis-related proteins (Bax, cleaved-caspase-3, and cytochrome C). Moreover, H/R results in a decrease in expression of anti-apoptotic protein (Bcl-2), which can be significantly attenuated with BTXA treatment. CONCLUSION: BTXA protects against apoptosis in HDMECs exposed to an in vitro model of H/R-induced injury.

Regional differences in facial skin blood flow responses to thermal stimulation.

PURPOSE: The facial skin blood flow (SkBF) shows regional differences in the responses to a given stimulation. The facial SkBFs, especially in the eyelid and nose exhibit unique response to physiological and psychological stimuli, but the mechanisms inducing those regional differences remain unclear. To investigate whether the regional differences in the local control of vasomotion in facial vessels correspond to the regional differences in facial SkBF response, we monitored the relative change of facial SkBF to regional thermal stimulation. We hypothesized that heat stimulation dilates the cutaneous vessels in the eyelid, while cold stimulation constricts those in the nose, which was based on previous findings METHODS: A thermal stimulator was used to apply temperature increase (from 20 to 40 °C at 2 °C/min) and decrease (from 40 to 20 °C at 2°C/min) in a randomized order to the right eyelid, nose, right cheek, and forehead of 14 healthy young males. The facial SkBF was measured for 10 s using laser-speckle flowgraphy when temperatures of 20 °C, 30 °C, and 40 °C had been applied for 30 s in both trials. RESULTS: The SkBF in the eyelid did not change significantly during any thermal stimulation, and the nasal SkBF did not decrease significantly during cold stimulation. The SkBFs in the cheek and forehead increased significantly with the applied temperature. CONCLUSIONS: These findings indicate that a large regional variation exists in facial skin blood flow response to local heating or cooling and that the regional variation did not correspond to the unique SkBF responses in the previous studies.

A Highly Selective Rho-Kinase Inhibitor (ITRI-E-212) Potentially Treats Glaucoma Upon Topical Administration With Low Incidence of Ocular Hyperemia.

Purpose: The purpose of this study was to investigate the IOP-lowering effects of the ITRI-E-212, a new Rho-associated protein kinase (ROCK) inhibitor. ITRI-E-212 improved fluid outflow through the trabecular meshwork and reduced IOP with transient and mild conjunctival hyperemia. ITRI-E-212 can potentially be developed into new antiglaucoma agents. Methods: ITRI-E-212 was selected from more than 200 amino-isoquinoline structures because of its adequate solubility and drug-loading percentage in eye drops. ITRI-E-212 has less than 50% inhibitory concentration (IC50) against ROCK2. The in vitro kinase inhibition was evaluated using the ADP-Glo kinase assay. A comprehensive analysis of the kinase inhibitor selectivity of ITRI-E-212 was performed using the KINOMEscan methodology. The IOP-lowering effect and tolerability of ITRI-E-212 were investigated in normotensive and ocular hypertensive rabbits. The pharmacokinetics study was performed in vivo in the aqueous humor (AH), and hyperemia was assessed. Results: ITRI-E-212 showed high in vitro inhibitory activity against ROCK2 and high specificity against AGC kinases. The mean IOP-lowering effect of ITRI-E-212 in normotensive and ocular hypertensive models was 24.9% and 28.6%, respectively; 1% ITRI-E-212 produced notable reductions in IOP that were sustained for at least 6 hours after each dose once per day. Only transient, mild hyperemia was observed. The compound extracted from the AH reached 78.4% ROCK2 kinase inhibition at 1 hour after dose administration and was sustained for 4 hours. Conclusions: ITRI-E-212 is a novel and highly specific ROCK2 inhibitor with the ability to lower IOP in animal models. It has favorable pharmacokinetic and ocular tolerability profiles with only minimal conjunctival hyperemia.

Functional reconstruction of total upper eyelid defects with a composite radial forearm-palmaris longus tenocutaneous free flap: A report of two cases.

This report presents reconstruction of wide- and full-thickness upper eyelid defects with a composite radial forearm-splitting palmaris longus tendon flap, which maintains eyelid opening and closing functions and supporting tissue in a Meibomian gland carcinoma in the right upper eyelid (case 1) and Merkel cell carcinoma in the right upper eyelid (case 2). After tumor resection with excisional margins, the defects involved the muscle, tarsal, and mucosa, with defect sizes of 60 × 40 mm and 85 × 40 mm, respectively. A radial forearm flap with the palmaris longus tendon was transferred. The tendon was split into two strips: the upper strip was fixed to the frontal muscles for the opening function and the lower strip to the medial palpebral ligament and orbicularis oculi muscle to maintain the closing function. Flap vessels were anastomosed to the superficial temporal artery and vein through the subdermal tunnel. Postoperative courses were uneventful. At the 5-year (case 1) and 4-year (case 2) follow-up periods, there were no tumor recurrence and keratalgia, and the eyelid opening and closing functions were maintained. This approach may contribute to achievement of not only the opening function but also the closing function of the reconstructed eyelid.

Bleomycin sclerotherapy for eyelid venous malformations as an alternative to surgery or laser therapy.

PURPOSE: To evaluate the clinical outcome of patients with venous malformation (VM) involving the eyelid treated with bleomycin sclerotherapy. METHODS: A retrospective review was performed of 18 consecutive patients with VM involving the eyelid who underwent bleomycin sclerotherapy. Patients' clinical presentation, details of sclerotherapy, and post-sclerotherapy resolution of the lesion as well as any procedure-related complications were evaluated. RESULTS: Twelve women and six men of mean age 34.3±20.4 years underwent sclerotherapy with bleomycin. Chief complaints were cosmetic disfigurations with or without hemifacial deformity (n=2), pain in engorgement area (n=2), pain and swelling from venous thrombosis (n=2), swelling or engorgement obstructing their eyesight (n=2), or eyelid dysfunction (n=1). The lesions were only in the eyelid in three patients; otherwise they were extended out of the eyelid either superiorly (n=3), laterally (n=8), inferiorly (n=8), and/or posteriorly to the orbit (n=8) to various extents. Conjunctival involvement was present in 13 patients. 14 patients had received prior treatments including surgery, laser therapy, or non-bleomycin sclerotherapy. With an average three sessions of bleomycin sclerotherapy (average total dose 34.5 mg), more than 80% shrinkage was observed in seven patients (38.9%), 50-80% shrinkage in eight patients (44.4%), and 30-50% shrinkage in two patients (11.1%). One patient had recurrence, which was successfully treated again with bleomycin. No procedure-related complications were noted. CONCLUSIONS: The use of bleomycin appears to be a simple, safe, and effective treatment for venous malformations involving the eyelid, avoiding more elaborate and challenging surgical or laser interventions, and is even effective in full thickness lesions.

Vitamin D Enhances the Efficacy of Topical Artificial Tears in Patients With Dry Eye Disease.

PURPOSE: To investigate the efficacy of topical carbomer-based lipid-containing artificial tears (CLAT) and hyaluronate (HU) in patients with dry eye disease (DED) based on serum 25-hydroxyvitamin D (25HD) levels and cholecalciferol (vitamin D) supplementation. METHODS: A total of 116 patients with DED from June 2015 to June 2016 were included. The participants were divided into the vitamin D deficiency (VDD) group and the non-VDD group according to their serum 25HD levels. The patients determined the ways of cholecalciferol supplementation. Ocular Surface Disease Index (OSDI) score, visual analog pain scale score, lid hyperemia, tear breakup time (TBUT), corneal fluorescein staining score, and Schirmer test were compared between baseline and 2 weeks posttreatment after topical applications and between before and after cholecalciferol supplementation. RESULTS: The OSDI and visual analog pain scale scores of both VDD and non-VDD groups decreased after application of topical CLAT and HU compared with baseline values (P < 0.05 for all, paired t test). TBUT, corneal fluorescein staining score, and lid hyperemia in the VDD group remained unaffected by topical CLAT and HU, whereas those in the non-VDD group were improved (3.2 ± 1.7 vs. 4.1 ± 2.2, 0.5 ± 0.7 vs. 0.4 ± 0.6, and 2.2 ± 0.8 vs. 1.9 ± 0.7 in the non-VDD group, P = 0.001, 0.030, and 0.012, respectively). OSDI score, TBUT, and lid margin hyperemia were improved in the intramuscular group after cholecalciferol supplementation compared with pretreatment (33.2 ± 23.2 vs. 28.5 ± 21.9, 3.5 ± 1.9 vs. 6.0 ± 2.5, and 2.2 ± 0.7 vs. 1.2 ± 0.8, P < 0.05, Wilcoxon rank test). CONCLUSIONS: The effect of topical CLAT and HU was dependent on serum 25HD levels. Cholecalciferol supplementation enhanced the efficacy of topical treatment and may be a useful adjuvant therapy for patients with DED refractory to topical lubricants.

Angular Vein Varix Congestion From Chronic Glasses Wear.

This is a case report of a symptomatic varicose angular vein exacerbated by chronic glasses wear. Compressing the vein in a recumbent position led to increased fullness of the medial canthal region and reproduced his symptoms. Obliteration by cauterization of the vein led to resolution of symptoms.

The Feasibility Determination of Risky Severe Complications of Arterial Vasculature Regarding the Filler Injection Sites at the Tear Trough.

BACKGROUND: The tear trough is a significant sign of periorbital aging and has usually been corrected with filler injection. However, the arterial supply surrounding the tear trough could be inadvertently injured during injection; therefore, this study aimed to evaluate the nearest arterial locations related to the tear trough and investigate the possibility of severe complications following filler injection. METHODS: Thirty hemifaces of 15 Thai embalmed cadavers were used in this study. RESULTS: The artery located closest to both the inferior margin (TT1) and mid-pupil level (TT2) of the tear trough was found to be the palpebral branch of the infraorbital artery. Furthermore, at 0.5 mm along the tear trough from the medial canthus (TT3), the angular artery was identified, which was found to be a branch of the ophthalmic artery. The artery at TT1 and TT2 was located beneath both the zygomaticus major and the orbicularis oculi muscles. The distances from TT1 to the artery were measured as follows: laterally, 2.79 ± 1.08 mm along the x axis; and inferiorly, 2.88 ± 1.57 mm along the y axis. For the TT2, the artery was located inferomedially from the landmark of 4.65 ± 1.83 mm along the x axis and 7.13 ± 3.99 mm along the y axis. However, the distance along the x axis at TT3 was located medially as 4.00 ± 2.37 mm. CONCLUSION: The high risk of injury to the artery at the tear trough should be considered because of the numerous arteries to this area.

Eyelid arteriovenous malformation treated with pre-surgical embolization: A case report.

Background Arteriovenous malformations are potentially serious vascular anomalies that are rarely encountered in the eyelid and require a multidisciplinary approach. Objectives We would like to describe the technical and clinical aspects related to the treatment of palpebral arteriovenous malformation with selective embolization, followed by surgical resection. Methods A 40-year-old patient presented with an isolated high-flow palpebral arteriovenous malformation. Transarterial embolization, using a liquid embolic agent (PHIL™), was performed in this patient. Results Angiographic and clinical follow-up revealed good results with clinical regression of the mass. Conclusion Although endovascular treatment of palpebral arteriovenous malformations is technically challenging, good functional and cosmetic result was achieved. Arteriovenous malformation embolization using PHIL™ seems to be very effective and makes subsequent surgical procedure safe and feasible. Level IV Evidence obtained from multiple time series with or without the intervention, such as case studies. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.