Disc Neovascularization Research Articles

Acute Retinal Necrosis: A Review of Diagnosis and Management

Acute retinal necrosis (ARN) is a profound infection of the retina, marked by acute panuveitis, retinal periarteritis, and widespread necrotizing retinitis. The etiology of ARN involves human herpesviruses, such as herpes simplex virus (HSV) and varicella-zoster virus (VZV), which can lead to severe visual impairment or even blindness. A diagnosis of ARN is based on clinical characteristics and disease progression according to the standard diagnostic criteria established by the American Uveitis Society (AUS) in 1994. The polymerase chain reaction(PCR) of aqueous specimens can enable identification of the type of virus. Early initiation of antiviral medication is essential for treatment efficacy to stop lesion progression, accelerate the healing process, and prevent contralateral eye involvement. Ocular complications of ARN include atrophic retina, multiple retinal breaks, rhegmatogenous retinal detachment (RRD), tractional retinal detachment (TRD), optic atrophy, macular edema, epiretinal membrane (ERM), and retinal and optic disc neovascularization. This review summarizes the clinical features, diagnostic criteria, and recently recommended ARN management.

The Spectrum of Presumed Tubercular Uveitis in a Referral Eye Clinic in Qatar

ABSTRACT Purpose To analyze the clinical spectrum of patients with presumed tubercular uveitis in a referral eye clinic in Qatar. Methods We retrospectively reviewed the clinical records of 50 patients (80 eyes) diagnosed with presumed ocular tuberculosis who presented to the uveitis clinic, department of Ophthalmology Hamad Medical Corporation, Qatar, from January 2014 till December 2019. Results Mean age at presentation was 34.5 ± 9.3 years. Forty one patients were males (82%) and 30 patients had bilateral involvement (60%). Forty eyes (50%) had posterior uveitis, 21 eyes (26.3%) intermediate uveitis, 11 eyes (13.7%) panuveitis, and 8 eyes (10%) anterior uveitis. Ocular findings included vitritis in 82.5% of eyes, retinal vasculitis in 46.3% (92% of which were occlusive in nature), multifocal choroiditis in 18.8%, serpiginous-like choroiditis in 11.3%, Most common complications at presentation or during follow-up included macular edema in 32 eyes (40%), preretinal or optic disc neovascularization in 29 eyes (36.3%) and vitreous hemorrhage in 17 eyes (21.3%). Anti-tubercular treatment was provided to 46 patients (92%). Systemic corticosteroids and corticosteroid sparing agents were associated, respectively, in 39 patients (78%) and 14 patients (28%). After 1 year of follow up, inflammation was controlled, with a significant improvement in visual acuity (p < 0.0001). Conclusions In Qatar, tubercular uveitis has a broad spectrum of ocular features, with posterior and intermediate uveitis being the most common anatomic forms. Vitritis, multifocal choroiditis without or with a serpiginous-like pattern, and occlusive retinal vasculitis are the most common ocular findings. Main sight-threatening ocular complications are macular edema, posterior segment neovascularization, and vitreous hemorrhage.

Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells.

Reabsorption of the nucleus pulposus (NP) in lumbar disc herniation (LDH) refers to the natural absorption or even complete disappearance of LDH. In order to better treat LDH, it is necessary to further study its mechanism and develop new therapeutic drugs. Clematidis Radix Et Rhizoma is a ranunculus family plant which has multiple biological activities, and Embinin is one of its bioactive ingredients. However, its effects on LDH were unclear. In this study, the role of Embinin was investigated in LDH rat models. LDH model was established by lumbar epidural insertion of tail disc. Our results showed that Embinin promoted lumbar disc neovascularization, induced apoptosis of NP cells in LDH rats, and promoted lumbar disc resorption. Furthermore, mechanistic study showed that Embinin activated the cAMP pathway in the rat models. In conclusion, Embinin has the potential to serve as a drug for the treatment of LDH.

Bilateral Florid Disc Neovascularisation in a case of CSCR

Purpose: To report NVD in a case of CSCR Method: CFP, OCT, FFA Result: Bilateral florid NVD in a case of CSCR Conclusion: Neovascularisation in CSCR is uncommon but can be managed actively to achieve optimal visual outcome.

Response to treatment of epiretinal neovascularization secondary to ischemic retinal vein occlusion in proliferative MacTel 2

Purpose: To describe a case of unilateral epiretinal neovascularization (ERN) secondary to an old ischemic retinal vein occlusion (RVO) in a patient with bilateral proliferative macular teleangiectasia type 2 (MacTel 2; Toto stage 4) and its response to treatment as documented by multimodal imaging. Methods: Retrospective case report Results: A 75-year-old woman with a six-year-history of MacTel 2 and the consecutive development of proliferative outer retinal neovascularization in both eyes over time presented with an ERN in addition to neovascularization of the optic disc, delayed filling of the retinal veins, peripheral capillary ischemia and intravitreal hemorrhage only in her left eye in September 2023. She was therefore treated with anti-vascular endothelial growth factor (anti-VEGF; aflibercept 2mg) intravitreally. The ERN responded well to a single intravitreal injection of anti-VEGF, while flow in the outer retinal proliferation persisted. Diagnosis and treatment with anti-VEGF were observed via optical coherence tomography angiography. Conclusion: We believe that the ERN formation was a reaction to ischemia of the inner retinal capillary plexus due to a preceding RVO. The herein presented case provides a new perspective on the development and treatment of ERN in MacTel 2.

A deep learning system for the detection of optic disc neovascularization in diabetic retinopathy using optical coherence tomography angiography images

A deep learning system for the detection of optic disc neovascularization in diabetic retinopathy using optical coherence tomography angiography images

Expeditious resolution of disc and iris neovascularization

Intraocular neovascularization is seen commonly as a response to retinal ischemia or less commonly due to inflammation. Inflammatory iris neovascularization responds well to topical steroids, whereas retinal neovascularization associated with uveitic conditions responds to systemic steroids or periocular depot injections. This case highlights an unusually rapid resolution of disc neovascularization along with iris neovascularization just with topical steroids in a middle-aged lady diagnosed with bilateral panuveitis and retinal vasculitis. We presume it may be due to a spontaneous decrease in posterior segment inflammation or due to systemic vascular remodeling.

Unilateral Optic Disc Neovascularization in a Patient with Optic Disc Pit Depending on Proliferative Diabetic Retinopathy

Unilateral Optic Disc Neovascularization in a Patient with Optic Disc Pit Depending on Proliferative Diabetic Retinopathy

Intravitreal bevacizumab causes rapid regression of disc neovascularization associated with large optic disk melanocytoma: a case report

Intravitreal bevacizumab causes rapid regression of disc neovascularization associated with large optic disk melanocytoma: a case report

Relationship Between Neovascularization of the Optic Disc and Diabetic Macular Edema.

Relationship Between Neovascularization of the Optic Disc and Diabetic Macular Edema.

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Background: Diabetic retinopathy is differentiated into two main types. They are non-proliferative and proliferative diabetic retinopathy. The presence or absence of aberrant new blood vessels is the differentiating characteristic between these two groups (retinal or optic disc neovascularization). The ischemic retina secretes vascular endothelial growth factor (VEGF). We conducted a study to evaluate the diabetic changes in the retina in type 1 diabetes mellitus (T1DM) after 15 to 20 years of its diagnosis using Fundus Fluorescein Angiography & Optical Coherence Tomography Angiography & Optical Coherence Tomography. Methods: The study was designed as a retrospective cohort clinical study conducted on T1DM patients. Results & Conclusion: The most frequent FFA finding was Microaneurysms (51.7%), followed by Cystoid macular edema (CME) (24.1%), while the least frequent findings were an artifact, neovascularization elsewhere (NVE), and branch retinal vein occlusion (BRVO) (3.4% for each). The most frequent OCTA finding was mean FAZ(0.32±0.09mm2) while mean SVD(46.2±4.6%) while mean DVD (46.1±5.6%).The most frequent OCT finding was epi-retinal membrane (16.7%), followed by exudate (13.3%) and intraretinal cyst (10.0%), while the least frequent finding was parafoveal macular edema (3.3%).

Алгоритмы искусственного интеллекта для диагностики признаков диабетической ретинопатии, диабетического макулярного отека, возрастной макулярной дегенерации, аномалий витреомакулярного интерфейса

Purpose. Development of artificial intelligence (AI) algorithms for diagnosing of diabetic retinopathy (DR), diabetic macular edema (DME), age-related macular degeneration (AMD), vitreomacular interface abnormalities (VMA) through the analysis of OCT scans and fundus images. Material and methods. Fundus images of patients with DR and DME, OCT scans of patients with DME, AMD and VMA were used as training and validation databases. The volume of training databases was 3600 fundus images and 10 000 OCT scans, the volume of validation databases was 400 fundus images and 1000 OCT scans. For fundus images analysis algorithms accuracy, sensitivity, specificity, AUROC were calculated for the following structures: microaneurysms, intraretinal hemorrhages, hard exudates, soft exudates, retinal and optic disc neovascularization, preretinal hemorrhages, epiretinal fibrosis, laser coagulates. For OCT scan analysis algorithms, these metrics were calculated for the features: intraretinal cysts, subretinal fluid, pigment epithelium detachment, subretinal hyperreflective material, drusen, epiretinal membrane, full thickness macular hole, lamellar macular hole, vitreomacular traction. Results. For fundus images analysis algorithms, accuracy exceeded 93% for all features except soft exudates (88.3%) and neovascularization (88.0%), sensitivity exceeded 90% for all features except neovascularization (80.2%) and epiretinal fibrosis (72.5%), specificity exceeded 91% for all features except microaneurysms (80.5%), hard exudates (83.5%) and soft exudates (88.7%), AUROC exceeded 0.90 for all signs except epiretinal fibrosis (0.88), neovascularization (0.87), preretinal hemorrhages (0.89). For OCT analysis algorithms, accuracy exceeded 93% for all features, sensitivity exceeded 90% for all features except lamellar macular hole (87.22%), specificity exceeded 93% for all features, AUROC exceeded 0.93 for all features. Conclusion. An algorithm for high precision segmentation of pathological signs has been developed. Based on these AI algorithms, the Retina.AI ophthalmological platform was developed, which allows automated analysis of OCT scans and fundus images and diagnosing of DR, DME, AMD and VMA. The platform is available for testing at https://www.screenretina.com/ Keywords: artificial intelligence, ophthalmic screening, diabetic retinopathy, diabetic macular edema, age-related macular degeneration, vitreomacular interface abnormalities

Optic nerve head perfusion changes in eyes with proliferative diabetic retinopathy treated with intravitreal ranibizumab or photocoagulation: a randomized controlled trial.

Proliferative diabetic retinopathy (PDR) is a serious sight-threatening disease, and half of the patients with high-risk PDR can develop legal blindness within 5 years, if left untreated. This study was aimed at comparing panretinal photocoagulation (PRP) and intravitreal ranibizumab injections in terms of radial peripapillary capillary (RPC) density on optical coherence tomography angiography (OCTA) in patients with treatment-naive PDR. This open-label, prospective, randomized clinical trial included 50 patients with treatment-naive PDR with optic disc neovascularization and randomized them into two groups: group 1, with patients undergoing two sessions of PRP 2 weeks apart, and group 2, with patients received three intravitreal ranibizumab injections (0.5 mg) 1 month apart for 3 consecutive months. Patients underwent a full ophthalmological examination, including best-corrected distance visual acuity (BCDVA) measurement in the logarithm of minimal angle of resolution (logMAR) notation and OCTA before intervention and monthly after the last laser session or the first intravitreal ranibizumab injection for 3 months of follow-up. Visual field (VF) was tested at the beginning and end of 3 months. Forty-two (84%) eyes completed the 3-month follow-up, including 22 eyes in the PRP group (88%) and 20 (80%) eyes in the ranibizumab group. The two groups were comparable in terms of demographic characteristics, diabetes duration, baseline BCDVA, glycated hemoglobin level, OCTA parameters, VF indices, and intraocular pressure (all P > 0.05). The RPC density change from baseline to the 3-month follow-up was significantly lower in the PRP group than in the ranibizumab group (mean difference in RPC density change: - 3.61%; 95% confidence interval: - 5.57% to - 1.60%; P = 0.001). The median (interquartile range) logMAR change from baseline to the 3-month follow-up (0.0 [0.2]) was significantly higher in the PRP group than in the ranibizumab group (- 0.15 [0.3]; P < 0.05). The median changes in central foveal thickness from baseline to the 3-month follow-up differed significantly between the two groups (P = 0.001). In eyes with PDR and neovascularization of the disc RPC density on OCTA increased in the ranibizumab group and decreased in the PRP group. Visual acuity gain was higher in the ranibizumab group than in the PRP group. Future multicenter trials addressing our limitations are required to verify the findings of this study.

A rare case of unilateral traumatic peripheral retinal arteriolar occlusions and neovascularization of optic disc

A young adult Asian Indian male presented to us with a 1-month history of trauma to the right eye (RE) with a tennis ball. He had intraocular pressure (IOP) of 32 mmHg while on three topical antiglaucoma drugs and oral acetazolamide, with uncontrolled inflammation in the anterior chamber (AC) and arteriolar occlusions in the periphery. His best corrected visual acuity was 20/20 in RE. Fluorescein angiography of the RE showed the presence of neovascularization of disc (NVD). Magnetic resonance angiography of the head and neck, and blood investigations ruled out the embolic origin of arteriolar occlusion and systemic causes for inflammation. Intra ocular pressure (IOP) and inflammation were controlled with appropriate treatment. NVD resolved with photocoagulation treatment (PRP) for capillary non-perfusion areas in 4 weeks. This case documents the occurrence of arteriolar occlusion, with neovascularization after arteriolar occlusion post blunt trauma, and successful adjunct use of topical cyclosporine in the management of AC inflammation and high IOP.

Hui Medicine Moxibustion Promotes the Absorption of Lumbar Disc Herniation and the Recovery of Motor Function in Rats through Fas/FasL Signaling Pathway.

Objectives To study the resorption of the herniated lumbar disc (RHLD) and its mechanism in the SD rats of lumbar intervertebral disc herniation treated with Hui medicine moxibustion (HMM). Methods Forty SD rats were randomly divided into four groups, normal group, lumbar disc herniation (LDH) group, HMM group, and antagonist (HMM+Met12) group, with 10 rats in each group. The rat model of LDH was prepared with the method of lumbar epidural emplacement of the caudal intervertebral disc. In the HMM group and HMM+Met12 groups, 4 weeks after modeling, HMM therapy was performed in the lumbar spine for 3 months with 1 time per day and 20 min each time, the samples were collected 8 weeks after the treatment. The histological degeneration was observed through HE staining, and the neovascularization of intervertebral disc tissues was detected by the expression of CD34 and vascular endothelial growth factor (VEGF). The apoptosis of nucleus pulpous cells was detected by TUNEL assay, and the activity of caspase-3, -8, and -9 and extracellular matrix enzymes was detected by western blotting. Results HMM treatment significantly improved the behavioral ability of rats with LDH surgery. The morphological structure was obviously destroyed in the LDH group, but disc structure was significantly repaired in the HMM group, and mild structure alterations were observed in the HMM+Met12 group. Higher levels of CD34 and VEGF were detected in the HMM group indicating that neovascularization is formed. The expression level of FasL was significantly increased in the HMM group. The protein expression levels of cleaved-caspase-3, cleaved-caspase-8, and cleaved-caspase-9 in nucleus pulposus (NP) tissues were also elevated when treated with HMM, and the TUNEL staining showed the same results. The protein expression levels of matrix metalloproteinases- (MMP-) 1, MMP-2, MMP-3, MMP-13, and ADAMTS-4 were markedly promoted in the HMM group. Met12, a small peptide antagonist of FasL, significantly reduced the effects of HMM. Conclusion HMM can promote the formation of neovascularization of lumbar intervertebral disc, support the apoptosis of NP cells through Fas/FasL signaling, and regulate the degradation of extracellular matrix enzyme, which then accelerates the absorption of lumbar intervertebral disc herniation and the recovery of motor function in rats.

Optical coherence tomography angiography for the detection and evaluation of ptic disc neovascularization: a retrospective, observational study

BackgroundTo assess and characterize neovascularization of the optic disc (NVD) using optical coherence tomography angiography (OCTA) and different OCTA-based methods.MethodsThis retrospective, observational study included patients who were suspected of having early PDR with no presence of clinically apparent neovascularization (NV) bur were clinically diagnosed with proliferative diabetic retinopathy (PDR), or severe NPDR. Patients underwent standard clinical examinations and OCTA imaging using a 6 × 6 montage scan. Two trained graders identified NVD using different imaging systems (ultra-widefield-colour fundus photography (UWF-CFP), OCT, OCTA and fluorescein angiography (FA)). Moreover, morphological classification of NVD was performed. The detection and morphological classification of NVD by different OCTA-based methods (B-scan OCTA, En-face OCTA, VRI Angio and VRI Structure) were compared.ResultsA total of 169 eyes (126 eyes with PDR and 43 eyes with severe NPDR) of 123 participants were included in this study. The detection rate of NVD was 34.91% by UWF-CFP compared with 59.76% by OCT, 59.76% by OCTA, and 62.72% by FA. After excluding 2 cases with epiretinal membranes, the NVD diagnosis detected by OCT was used as the standard. Among 99 eyes diagnosed with NVD by OCT, B-scan OCTA detected NVD with a sensitivity of 97.98%, which was higher than that by en face OCTA (80.81%), VRI Angio (65.66%), and VRI Structure (61.62%) (all P < 0.05). According to its characteristics on OCTA, NVD was divided into four types (12 cases of type I, 6 cases of type II, 39 cases of type III, and 42 cases of type IV). For type I, B-scan OCTA exhibited a higher diagnostic sensitivity than other methods (P < 0.05). For types II and IV, there were no statistically significant differences in the sensitivity of various methods between the two groups (P > 0.05).ConclusionOCTA and different OCTA-based methods are significant to the diagnosis of NVD, and the diagnostic accuracy of different detection methods may be related to different types of NVD.

Optic disc neovascularization in panuveitis and the role of optical coherence tomography angiography in diagnosis and follow-up

Optic disc neovascularization in panuveitis and the role of optical coherence tomography angiography in diagnosis and follow-up

Recurrence of Lymphoblastic Leukemia Manifesting as Bilateral Optic Disk Neovascularization During Complete Clinical Remission--Case Report

<i>Background</i>: The intraocular manifestations of leukemia are diverse. The retina is the most common ophthalmic involvement site. The most common retinal manifestations of acute lymphoblastic leukemia (ALL) include dilated and tortuous vessels, serous retinal detachment (SRD), intraretinal hemorrhages as well as roth spots. Optic nerve infiltration and retinal neovascularization are unusual, especially in complete clinical remission of ALL. However, neovascularization in optic disk has not been observed in ALL during complete clinical remission. <i>Objective</i>: To report clinical characteristics of a bilateral optic disk neovascularization associated with relapse of ALL. <i>Method</i>: A 31-year-old male with ALL after having reached complete remission from chemotherapy complained about a vision loss in both eyes. First examination showed that best corrected visual acuity (BCVA) was 20/200 for his right eye and 20/160 for his left eye, respectively. Fundus examination revealed bilateral profound optic disk edema with multiple yellow-white exudates and retinal hemorrhages. Optical coherence tomography (OCT) showed bilateral optic disk edema and SRD in both maculas. Fundus fluorescein angiography (FFA) showed bilateral optic disk neovascularization. All these changes were present in remission. The patient received intravitreal Conbercept injection 0.5 mg (10 mg/ml) in both eyes for once on June 29, 2019. Optic disk neovascularization resolved three weeks after treatment. BCVA improved to 20/200 in his right eye, but still light perception in his right eye. No optic disk neovascularization recurrence was observed in 3-month follow-up. BCVA of the right eye maintained 20/200 at the latest follow-up. After intravitreal injection for 4 months the patient suffered from cerebral hemorrhage. He received bone marrow biopsy and cerebrospinal fluid sampling. The results showed relapse in hemogram and lymphocytes in central nervous system (CNS). Therefore, the chemotherapy treatment did not cause a new remission of the disease and the patient failed to recover. <i>Conclusion</i>: Optic disk neovascularization may appear as a sign of extramedullary relapse of ALL months in advance of the hematologic relapse. Intravitreal injection of conbercept could be beneficial and safe in treating this neovascularization.

Application of iris angiography combined with ultra-wide-field fundus fluorescein angiography in diabetic retinopathy

Objective: To explore the application and value of iris angiography combined with ultra-wide-field fundus fluorescein angiography (UWFA) in diabetic retinopathy (DR). Methods: This was a cross-sectional study. From May 2016 to December 2019, 60 consecutive DR patients (120 eyes) including 30 patients (60 eyes) with severe non-proliferative DR (NPDR) and proliferative DR (PDR), respectively, who underwent iris angiography combined with UWFA in Tianjin Medical University Eye Hospital were enrolled in the study. There were 25 males and 35 females, with an average age of (53.5±10.7) years. All of the patients underwent ophthalmologic examination including visual acuity, intraocular pressure, slit-lamp microscopy, slit-lamp funduscopy, ultra-wide-field fundus photography, and iris angiography combined with UWFA. Iris angiography included iris fluorescein angiography (IFA) and iris indocyanine green angiography. The onset time of the iris vascular fluorescein leakage was recorded, and the circumference range of the pupil margin fluorescein leakage was measured by a self-developed software. Wilcoxon rank sum test was used to compare and analyze the difference in the onset time and the range of the iris vascular fluorescein leakage between the severe NPDR and PDR groups. Results: IFA showed that the onset time of the iris vascular fluorescein leakage was 31.00 (25.75, 34.00) s and 27.00 (21.75, 29.50) s in the severe NPDR group and the PDR group, respectively. The difference between two groups was statistically significant (Z=-2.13, P=0.033). The range of the iris vascular fluorescein leakage was 20.00(10.75, 75.00)° and 135.00(60.00, 182.50)° in the severe NPDR group and the PDR group, respectively. There was significant difference between two groups (Z=-4.23, P<0.001). Neovascularization of the iris was not found in all patients with PDR by slit-lamp microscope examination, but was found in 8 eyes by IFA and iris indocyanine green angiography. UWFA findings demonstrated that there was no strong fluorescence in retinal neovascularization elsewhere and/or neovascularization of the optic disc in severe NPDR patients. However, that could be seen in all PDR patients. Among them, 10 eyes had terminally petaloid or focal fluorescein leakage in macular area. Conclusions: Iris angiography combined with UWFA and quantitative analysis method could not only accurately assess the degree of fundus lesions, but also obtain more accurate and comprehensive iris vascular information, which provided help for comprehensive and personalized treatment of DR. (Chin J Ophthalmol, 2021, 57: 916-921).

Sensitivity and specificity of MultiColor imaging in detecting proliferative diabetic retinopathy.

PurposeTo evaluate the accuracy of MultiColor imaging (MC) compared to fluorescein angiography (FA) in detecting proliferative diabetic retinopathy (PDR) and associated diabetic retinopathy features.MethodsFifty-nine eyes from 38 PDR patients were included. MC images were reviewed by 2 independent masked graders. A qualitative analysis based on the following features was performed: neovascular complexes (NVC), disc neovascularization (NVD), neovascularization elsewhere (NVE), microaneurysm (MA), intraretinal hemorrhage (IRH), vitreous hemorrhage (VH), preretinal hemorrhage (PRH), fibrosis, hard exudates (HE), epiretinal membrane (ERM), diabetic macular edema (DME), ischemia and laser spots (LS). Measures of diagnostic accuracy compared to FA were determined.ResultsThe sensitivity for the detection of NVC using MC was 95.1%, with a specificity of 40.0%, positive predictive value (PPV) of 92.9% and negative predictive value (NPV) of 50.0%. Sensitivity and specificity were higher in detecting NVD (88.9% and 76.9%) while NVE registered higher PPV (88.9%). MC was highly sensitive in detecting IRH, HE, ERM and LS (100%), MA (98.0%) and fibrosis (95.5%). Highest specificity was found for VH (100.0%), DME (100.0%), PRH (98.1%) and LS (89.5%). The area under the receiver-operating characteristic analysis of MC was excellent in NVD (0.83, 95% confidence interval (CI), 0.71–0.95, p < 0.001), IRH (0.89, 95% CI 0.74–1.00, p < 0.001), VH (0.81, 95% CI 0.60–1.00, p = 0.005) and PRH (0.89, 95% CI 0.68–1.00, p = 0.004) and outstanding in LS detection (0.95, 95% CI 0.87–1.00, p < 0.001). These results are likely due to the contrast and quality of the MC since better discrimination is enabled by the green wavelength.ConclusionMC is useful in evaluation of PDR patients and can complement noninvasive imaging. MC detected some PDR features more accurately than FA such as NVD, IRH, VH, PRH, and LS.