Biomedical subjects

M Knorr

Publications and source records attributed to M Knorr.

At least 37 records · Page 2Linked to original sources

PubMed1998

[Review of general anesthesia procedures in ophthalmology].

We review the anaesthetic management of patients undergoing ophthalmic examination or surgery. General anaesthesia is administered in patients demanding immobilisation, since uncontrolled movement may rise intraocular pressure (IOP) and thus endanger the overall outcome of ophthalmic care. We discuss the effects of anaesthetics and anaesthesia related medications on IOP before, during, and after eye surgery. Also, we analyse anaesthetic procedures applied in eye injury management, vitreal and strabismus surgery as well as paediatric ophthalmology. Finally, we review the systemic side effects of topical eye medications, the complications of ophthalmic general anaesthesia as well as their prevention.

Anesthesia, General↗

PubMed1997

Proliferative response of cultured human tenon's capsule fibroblasts to platelet-derived growth factor isoforms.

BACKGROUND: Although platelet-derived growth factor (PDGF) has been thought to be critical in the wound-healing response of Tenon's capsule fibroblasts after glaucoma filtration surgery, no information is currently available concerning the proliferative effect of PDGF isoforms on this cell type. The aim of the present study was to evaluate the proliferative effect of PDGF-AB heterodimer and PDGF-AA and -BB homodimers on cultured human Tenon's capsule fibroblasts. METHODS: Human Tenon's capsule fibroblasts, cultured under serum-free conditions, were stimulated with PDGF-AA, -AB and -BB isoforms in concentrations ranging from 1 to 100 ng/ml. Cell numbers were determined on days 1, 3, 5 and 7, using a cell counter. RESULTS: Addition of PDGF-AB and -BB led to a dose-dependent increase in cell proliferation. A maximal response (79.9% over control) was obtained after 7 days with 30 ng/ml of PDGF-BB, with an EC50 of 8.9 ng/ml. The maximal increase in cell proliferation caused by PDGF-AB (30 ng/ml) was 54.9%, with an EC50 of 12.5 ng/ml. Stimulation with PDGF-AA revealed a significant effect only with concentrations higher than 30 ng/ml. CONCLUSION: Our results indicate that PDGF-AB and -BB isoforms are potent stimulators of proliferation of human Tenon's capsule fibroblasts, suggesting that PDGF-AB and -BB isoforms play an important role in the wound-healing response after glaucoma filtration surgery.

Anticoagulants↗

PubMed1997

The in vitro effect of platelet-derived growth factor isoforms on the proliferation of bovine corneal stromal fibroblasts depends on cell density.

PURPOSE: Recently, it has been shown that corneal stromal fibroblasts express the mRNA for PDGF-beta-type receptors, while corneal epithelial cells express the mRNA for the PDGF B-chain, suggesting a role of PDGF isoforms in the regulation of corneal homeostasis and wound healing via an unidirectional epithelial to stromal paracrine interaction. The purpose of this study was to characterize the proliferative response of cultured bovine corneal stromal fibroblasts to PDGF isoforms. METHODS: Bovine corneal stromal fibroblasts were seeded at a cell density of 60 cells/mm2 (low density) and 120 cells/mm2 (high density) and were cultured under serum-free conditions. Except for corresponding controls, PDGF AA, BB and AB (obtained by separate expression of cloned genes in E. coli) were added in concentrations ranging from 3.125 to 100 ng/ml. Cell numbers were determined after an incubation period of 6 days using a cell counter. RESULTS: Stromal fibroblasts, when cultured at a high density, revealed constant cell numbers during the whole incubation period. Under these culture conditions, stimulation with PDGF AA, BB and AB led to a significant dose-dependent increase in cell proliferation. When cultured at a low cell density, stromal fibroblasts revealed a significant reduction of cell numbers after 6 days of incubation. This reduction was prevented by PDGF AA and AB isoforms in a dose-dependent manner. In contrast, PDGF BB was not effective. CONCLUSION: The results of the "high-density" assays suggest that PDGF isoforms act as mitogens for stromal fibroblasts during wound healing, when density of fibroblasts is high. The results of the "low-density" assays support the idea that PDGF AA and AB can prevent cell loss during corneal homeostasis when density of keratocytes is low.

Animals↗

PubMed1997

[Lens coloboma and lens dislocation in Stickler (Marshall) syndrome].

BACKGROUND: Both, Stickler and Marshall syndrome are dominantly inherited, connective tissue disorders with highly variable individual manifestations. Probably, both syndromes represent the same entity with occasional partially different clinical manifestations. PATIENT: We are reporting on a female patient with typical ocular and systemic manifestations of both syndromes: high myopia, glaucoma and goniodysgenesis, submucosal cleft palate, sensorineural hearing loss, and "flat" mid-face. Additionally, we observed subluxation of the ocular lens in one eye which was previously described in only a few cases. In our case, subluxation was combined with nasal coloboma of the lens and congenital cataract. This represents the first report of coloboma of the ocular lens as a manifestation of Stickler (Marshall) syndrome. In both children of the patient manifestations of the syndrome were present (high myopia, cleft palate, sensorineural hearing loss). CONCLUSION: Coloboma and subluxation of the lens have to be regarded as possible manifestations of the Stickler (Marshall) syndrome. The syndrome(s) should be included in the differential diagnosis of ectopia lentis-associated systemic diseases.

Abnormalities, Multiple↗

PubMed1997

[Effectiveness of dorzolamide as added therapy in glaucoma patients with maximum tolerated drug therapy. A pilot study].

BACKGROUND: The purpose of this study was to evaluate prospectively the value of dorzolamid as an adjunct to maximum tolerated medical therapy in glaucoma patients in whom surgery would otherwise be required. METHODS: 32 eyes of 21 patients with primary open angle glaucoma (14 patients), glaucoma in aphakia (3 patients), pigmentary glaucoma (2 patients), juvenile glaucoma (1 patient) and exfoliative glaucoma (1 patient) were included. The effect of additional dorzolamid application on intraocular pressure (IOP) was determined after 2 hours, 4 days, 4 weeks, 3 months and 6 months. After 6 months, visual fields were checked. RESULTS: Average reduction of IOP in eyes in which dorzolamid was continued was determined to be 31% after 2 hours, 18.3% after 4 days, 17.9% after 4 weeks, 12.1% after 3 months and 9.7% after 6 months. 19 (59%) eyes continued to receive dorzolamid after 6 months without being operated. No progression of glaucomatous damage could be detected in these eyes. In 11 (34%) eyes, treatment with dorzolamid was discontinued. 2 patients (4 (12%) eyes) did not tolerate local side effects of dorzolamid. In 7 (22%) eyes reduction of IOP was insufficient and filtration surgery had to be performed immediately. CONCLUSION: The results of the present study demonstrate that dorzolamid represents an alternative to an immediate surgical management in patients on maximum tolerated therapy for at least six months.

Adult↗

PubMed1997

[Phototoxic maculopathy after arc welding: value of multifocal ERG].

BACKGROUND: Phototoxic maculopathy most likely results from longer exposure to light from sources such as the sun, welding arcs, tungsten halogen lamp filaments or operation microscopes. The value of the multifocal ERG for the evaluation of functional defects in this rare entity has not been described to date. CASES: We describe the case of a 38-year-old male patient who presented to his local ophthalmologist with bilateral loss of vision and acute ocular pain after having worked for two hours at an electric welding arc. A foveal lesion was found in both eyes, resulting in a bilateral reduction of visual acuity. Nine months later, the patient underwent examination and further investigations at the university eye clinic in Tübingen. Visual field defects on both sides could be detected with automatic threshold perimetry. Using the multifocal ERG with a central element of 2 degrees diameter, a central defect was detected only for the right eye. CONCLUSIONS: In rare cases, a photic maculopathy can result from exposure to light during arc welding. It can be masked in the first days by a phototoxic keratitis. Multifocal ERG and automatic perimetry are useful tools for the detection and quantification of the functional defects.

Adult↗

PubMed1997

[Diode laser cyclophotocoagulation in treatment of therapy refractory glaucoma].

BACKGROUND: It has been suggested that Nd:YAG laser cyclophotocoagulation significantly lowers the intraocular pressure in refractory glaucoma. However, only limited information is currently available concerning the cyclodestructive effects of diode laser cyclophotocoagulation. PATIENTS AND METHODS: Twenty eyes of 17 patients had undergone diode laser cyclophotocoagulation if previous glaucoma surgery including cyclocryocoagulation was unsuccessful or the patients were blind. Nine eyes had secondary glaucoma, 5 neovascular glaucoma, 5 congenital glaucoma, and 1 eye chronic open angle glaucoma. Treatment was applied in two quadrants using a 810 nm diode laser (600 qm diameter quartz fiber, 2 sec, 1.75-3 W, 6 to 10 pulses). Seven eyes required retreatment. RESULTS: In 19 eyes the baseline IOP was 32.1 +/- 10.1 mm Hg and at the patient's last examination 21.0 +/- 8.4 mm Hg. Median follow up was 11 months (3 to 19 months). In 4 of 5 eyes with a visual acuity of less than 1/50 IOP was decreased under 30 mm Hg, while 9 of 14 eyes with a visual acuity of at least 1/50 IOP revealed a decrease of IOP under 20 mm Hg, resulting in a success rate of 68%. Complications included acute severe anterior uveitis in one eye and bulbus hypotonia in another for several months. After three weeks, one eye was enucleated because of persisting high IOP and pain. Histopathologically, coagulation necrosis of the ciliary body stroma and separation of epithelial layers were observed. CONCLUSIONS: This study suggests that contact diode laser cyclophotocoagulation is an effective method and a valid alternative to cyclocryocoagulation in the treatment of refractory glaucoma including congenital glaucoma.

Adolescent↗

PubMed1997

Regional glycoprotein expression in the chicken lens.

PURPOSE: Several previous studies have shown that glycoconjugates of extracellular matrix, cell membrane and nucleus play an important role in the mediation of cell proliferation, migration and differentiation. Lens epithelial cells and lens fiber cells show regional differences with regard to these parameters. If glycoconjugates participate in the regulation of these patterns in the lens, there should be regional differences in the expression of glycoconjugates. The investigation was focused on the anterior pole, equator and nuclear bow regions, which differ extensively in lens cell proliferation and differentiation. METHODS: To check this hypothesis, the regional binding pattern of twelve different FITC-conjugated lectins was studied glycohistochemically, using paraffin embedded material. The investigation was focused on the anterior pole, equator and nuclear bow regions. RESULTS: Regional differences in lectin binding patterns were identified in the lens capsule, epithelium and the nuclear bow regions. The lens capsule was fluorescently labeled with GS-I, UEA-I, LPA, MAA, SNA only at the anterior pole and with CON-A, WGA, DBA, SBA only at the equator. Staining of the entire anterior surface of the lens capsule was observed with LFA. Cell membranes of the lens epithelium showed binding of MAA and LFA only at the equator. LFA, LPA, MAA and SNA only stained the nuclei of fiber cells at the nuclear bow region but not of lens epithelial cells. WGA strongly labeled the nuclei of equatorial epithelial cells and fiber cells at the bow region. CONCLUSIONS: It is assumed that the observed regional variations in glycoprotein expression in the extracellular matrix and lens cells contribute to the regulation of cell behavior in different areas of the lens.

Animals↗

PubMed1996

[Autologous conjunctiva-limbus transplantation in treatment of primary and recurrent pterygium].

The aim of the present study was evaluation of the efficiency of limbal autograft transplantation for primary and recurrent pterygia. The results of limbal autograft transplantation for advanced and recurrent pterygia are presented for 58 eyes of 50 patients. The pterygia were primary in 40 eyes and recurrent in 18 eyes. Free grafts from the superotemporal limbus of the same eye were used to cover the exposed sclera. Postoperative followup ranged from 2 to 26 months, with a mean of 13 months. The overall recurrence rate was 31% (22.5% in primary pterygia and 50% in recurrent pterygia). Recurrence rates were significantly higher in patients from southern Europe than in patients from northern Europe. Analysis of patients with recurrences (n = 18) revealed severe tear film abnormalities in eight cases. Seven patients were found to have transplants of insufficient size. Analysis of our results provides evidence that the experience of the surgeon is crucial for the success rate of this procedure. Three of six surgeons with limited experience had a recurrence rate of 50% or more. Additionally, 15 patients who developed recurrent pterygium had returned to unfavourable working conditions (e.g. dust, heat). Three of the 18 recurrences underwent repeated limbal transplantation and in one of these there was a further recurrence.

Adult↗

PubMed1996

[Effect of heparin and ascorbic acid on growth behavior of cultivated corneal epithelial cells of the rabbit].

Although ascorbic acid and heparin are used for local therapy of corneal wounds that heal poorly (e.g., after chemical burns), little has been known up to now about the mechanisms underlying their effectiveness at the cellular level. The aim of the present study was therefore to evaluate the effect of heparin and ascorbic acid on the growth behaviour of corneal cells in vitro. For this purpose cell cultures from a corneal epithelial cell line were used. Stimulation of the cells with heparin at concentrations ranging from 10 to 200 micrograms/ml for 6 days led to a dose-dependent rise in growth rate (population doublings per day) of 0.48 +/- 0.50 to 2.19 +/- 1.65 (mean value +/- standard deviation, n = 10) with an EC50 of 132 micrograms/ml. In contrast, the addition of ascorbic acid at concentrations ranging from 0.5 to 3.0 mM led on average to a 40% dose-dependent inhibition of cell proliferation after 6 days, with an IC50 of 0.7 mM as-corbic acid. On the basis of these results, the use of heparin at concentrations of 180-200 micrograms/ml appears advantageous. In contrast, the local application of ascorbic acid for chemical burns with no stromal involvement should be subjected to a critical reassessment.

Animals↗

PubMed1996

Lacrimal secretion of human epidermal growth factor in perforating keratoplasty.

Human epidermal growth factor (hEGF) plays a key role in the regulation of corneal epithelial regeneration. As the lacrimal concentration of EGF is known to decrease following corneal injury, therapeutic application of exogenic EGF to support corneal wound healing is currently being investigated. To evaluate the role of topical EGF substitution in perforating keratoplasty, the lacrimal secretion of EGF was determined in 12 patients prior to keratoplasty and on the 1st and 7th days postoperatively using a newly developed modular immunofluorometric assay. EGF secretion and tear-flow rates in the tear samples of the keratoplasty patients were compared with those of 39 patients with corneal epithelial defects of other origin and those of 21 healthy controls. Levels of EGF secretion and tear flow reflectorily increased both in the post-operative samples of keratoplasty patients (secretion 0.77 +/- 0.56 pg/s, tear flow 18.7 +/- 14.9 microliter/min) and in the samples of patients with corneal epithelial defects (0.6 +/- 0.4 pg/s, 19.6 +/- 19.2 microliter/min) in comparison with preoperative values and healthy controls (0.3 +/- 0.2 pg/s, 4.0 +/- 5.4 microliter/min). Men showed higher average levels of basal and reflectory EGF secretion (0.4 and 0.8 pg/s), respectively than did women (0.25 and 0.55 pg/s, respectively). The results indicate a physiological feedback mechanism that reflectorily adjusts the lacrimal EGF secretion following corneal irritation. Topical therapy with recombinant EGF should therefore be restricted to patients with persistent corneal epithelial defects and proven deficiency of EGF secretion.

Adult↗

PubMed1995

The Tübingen Glaucoma Study. Glaucoma filtering surgery--a retrospective long-term follow-up of 254 eyes with glaucoma.

A major focus of our study was the ability to predict the long-term success of filtering surgery. The results of glaucoma filtering surgery (trabeculectomy) as performed by the staff of the University Eye Hospital of Tübingen from 1988 through 1994 on 254 eyes of 214 patients are presented, with particular emphasis being placed not only on intraocular pressure (IOP) control but also the progression of glaucomatous damage (visual field loss or disc damage) and the etiology of visual acuity losses. There was an overall success rate of 64%. Rigid criteria for success included an IOP of less than 30 mmHg, no further visual field loss or disc damage, and no glaucomatous etiology for a decrease in visual acuity. A total of 35 eyes (13.8%) showed a loss of visual acuity after 6 months amounting to 2 or more Snellen lines, caused mainly by lens opacification, hypotony maculopathy, and "wipeout" (loss of the central visual field in the absence of another explanation). We found that there is a considerable risk for sudden loss of visual acuity after operation on older patients with small residual visual fields and severe hypotony on the 1st postoperative day. There was a 13% incidence of failure of blebs. A total of 34 eyes had an early IOP rise of more than 30 mmHg after surgery. A postoperative hypotony of less than 3 mmHg was more significantly seen in patients treated with 5-fluorouracil. Moreover, the results show that in some instances, a long-term use of topically applied glaucoma medication can adversely affect the results of fistulizing surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

[Predicting recurrent pterygium based on morphologic and immunohistologic parameters].

BACKGROUND: Independently of the technique for excision used, pterygia recur quite frequent. We investigated whether recurrences can be predicted by means of histological and immunohistological parameters. MATERIALS AND METHODS: In a prospective clinical investigation the frequency of recurrent pterygia after excision and subsequent autologous limbal grafting was studied. The pterygia of 10 patients without recurrence (mean follow-up time 13 months) were compared retrospectively and semiquantitatively with the pterygia of 7 patients who had a recurrence. The following parameters were taken into consideration: (1) elastoid degeneration; (2) amount of vascularization; (3) morphological signs of "dry eye" (e.g., loss of goblet cells, beginning keratinization); (4) reactive inflammation; (5) amount of CD1a-, CD4-, CD8- and CD68-positive cells; (6) expression of PDGFalpha, PEDGFbeta, EGF, and laminin receptors. RESULTS: No appreciable differences between recurrent and nonrecurrent pterygia were found. CONCLUSION: As adjuvant therapeutic strategies like application of mitomycin C or beta-irradiation may lead to complications, it would be desirable it they could be limited to patients at risk. The histological and immunohistological parameters investigated probably do not allow prediction of pterygial recurrence. Consequently, they are not helpful in deciding whether adjuvant therapy should be started or not.

Adult↗

PubMed1995

[Photodynamic activity of phthalocyanines in cultivated lens epithelial cells of the pig].

One of the most frequent complications of extracapsular cataract surgery is posterior capsule opacification (PCO), which is caused by proliferation and migration of retained lens epithelial cells on the posterior capsule surface. This complication leads to a reduction in visual acuity. Depending on the age of the patients, the incidence varies between 15 and 50%. Selective elimination of these cells would therefore prevent PCO. Phthalocyanines (Pc) are efficient photosensitizers of various carcinoma cell lines. Their attractive property is the strong absorption of visible light above 600 nm. Upon absorption of a photon, the sensitizer in its excited state can be either directly cytotoxic or produce reactive oxygen species type I (free radicals) or type II (singlet oxygen), which become the mediator of cellular injury by affecting membranes and subcellular organelles. Preconfluent cultures of porcine lens epithelial cells were incubated with aluminum phthalocyanine (AlPc) or aluminum phthalocyanine transulfonate (AlPcS4) in concentrations ranging from 0-20 microM for 1 h at 37 degrees C. Thereafter, cultures were exposed to red light for 5 min. A 300 W quartz halogen light bulb equipped with a cut-off filter that allowed transmission of the whole spectrum above 600 nm was used for activation of the sensitizers. To evaluate the effect of fluoride, 5 mM NaF was added to the dye-loaded cells immediately before light exposure. This treatment had no toxic effect. Subsequently, the treated cells were incubated in culture medium for 24 h. After trypsinization, the cell number was determined by a cell counter. Prior to light exposure neither AlPc nor AlPcS4 was toxic in corresponding controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

[Age-dependent distribution of Langerhans cells within human conjunctival epithelium].

Non-pathological conjunctival specimens (240) were used for evaluation of Langerhans cell (LC) numbers per square millimeter. Of the 240, 60 were taken from each of four age groups (1-20 years, 21-40 years, 41-60 years, 61 years and older). In each group, 20 came from the bulbar conjunctiva (lateral superior), 20 from the fornix region (central superior), and 20 from the palpebral conjunctiva (central inferior). Quantitative analysis was carried out with the Langerhans-specific anti-CD1a antibody using APAAP method. Additionally, 40 conjunctival specimens were stained with the Tü 36 (all HLA/DR Ag) and the Tü 39 (all HLA/DR, -/DP Ag). A basic decline in the density of LC cells corresponding to advancing age of the tissue donors was found in all three regions studied (< or = 20 years: 4.4 LC/mm2; > 60 years: 1.2 LC/mm2). The largest number of LC (4.7 LC/mm2) was found in the palpebral conjunctiva (central inferior); 3.1 LC/mm2 were found in the fornix (central superior) and 1.0 LC/mm2 in the bulbar conjunctiva (lateral superior). As an antigen-presenting cell, the LC plays an important role in immune reactions in the area of the superficial ocular epithelium. The data gained here can serve as a basis for studies of pathological tissue since, as is known from dermatological research, firm relationships exist between specific inflammatory or tumorous diseases and LC density in the affected organs. Moreover, a direct connection is to be assumed between the success of transplantation and LC density in allogenic conjunctival grafts.

Adolescent↗

PubMed1995

[PDGF-induced effect on cytosolic free calcium concentration of cultured retinal pericytes].

Although the selective loss of retinal pericytes has long been known to be one of the earliest histopathological findings in diabetic retinopathy, only limited information is available concerning their function and cell biology. Recently, it has been shown that the interaction of endothelial cells and pericytes plays an important role in the maintenance of vascular integrity. Additionally, it has been suggested that pericytes have a contractile function. Platelet-derived growth factor (PDGF), released from endothelial cells, has been shown to be a potent mitogen and vasoconstrictor. Cytosolic free calcium ([Ca2+]i) has been shown to play a key role as a second messenger for PDGF, involved in the regulation of various cellular functions, e.g. cell proliferation and vascular contractility. In order to characterize the effect of different PDGF homodimers on cultured bovine retinal pericytes, we investigated PDGF-AA- and -BB-dependent alterations in [Ca2+]i was determined with the Ca(2+)-sensitive fluorescent probe Quin-2. Basal levels were 118 +/- 30 nM. Stimulation with PDGF-BB in concentrations ranging from 5 to 20 ng/ml led to a dose-dependent increase of [Ca2+]i with an EC50 of 5.8 ng/ml. Maximum stimulation, to about 280% of basal levels, occurred after 3-4 min. In contrast, PDGF-AA was not effective. The results suggest that PDGF-BB may influence the integrity and contractility of the retinal microvasculature via modulation of the intracellular calcium homeostasis of pericytes. Additionally, it can be speculated that cultured retinal pericytes express mainly PDGF-beta-type receptors.

Animals↗

PubMed1994

Autoinhalation of nitric oxide after endogenous synthesis in nasopharynx.

Exogenous nitric oxide (NO) reduces pulmonary vascular resistance after low-dose inhalation in patients. To estimate endogenous NO synthesis in the upper respiratory tract, we measured inhaled and exhaled NO in volunteers and patients during spontaneous or controlled ventilation, respectively. 20.3 nmol per min NO was synthesised in the nasopharynx of non-smoking volunteers, leading to autoinhalation of 0.07-0.13 NO parts per million during inspiration; smokers had reduced NO synthesis. In volunteers, 50-70% of the NO was resorbed by the lungs; ventilated patients were deprived of NO autoinhalation. Bacteria in the nose may take part in endogenous NO synthesis.

Adolescent↗

PubMed1994

Serum-free cultivation of bovine lens epithelial cells.

Mammalian cells in culture have individual nutritional requirements which are mainly fulfilled by the addition of fetal calf serum to the basic culture medium. Since many of the serum components are as yet poorly understood or even completely unknown, a number of difficulties arise in the evaluation of the effect of exogenously added factors or drugs on the growth of the cells. This paper presents data demonstrating the successful adaptation, routine cultivation and cryopreservation of bovine lens epithelial cells (BLEC) under serum-free culture conditions by use of the commercially available serum substitutes BMS, BM-86 Wissler and Ultroser G. Moreover, a culture medium especially designed for cell quiescence, named LR-1, is presented. Cells cultivated in culture medium containing 10% fetal calf serum served as controls. While BM-86 Wissler caused significantly reduced growth rates within 2 days and, finally, cell death after 12 days of incubation, the use of BMS resulted in growth rates which did not differ from the corresponding controls. Ultroser G resulted in a significant increase of proliferative activity of BLEC. LR-1 medium caused cell quiescence and kept the cells alive for a number of days. Thus, LR-1 allowed evaluation of the response of the cells to a mitogenic mixture from bovine brain mainly containing endothelial cell growth factor. The results demonstrate that cultivation of BLEC is possible under serum-free culture conditions. Moreover, the medium LR-1, which causes cell quiescence, is useful for the evaluation of growth factor-induced effects in vitro.

Animals↗