Mutations in C2ORF71 cause autosomal-recessive retinitis pigmentosa.

With a worldwide prevalence of 1 in 4,000, retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration. More than 30 genes and loci have been implicated in nonsyndromic autosomal-recessive (ar) RP. Genome-wide homozygosity mapping was conducted in one Dutch and one Israeli family affected by arRP. The families were found to share a 5.9 Mb homozygous region on chromosome 2p23.1-p23.3. A missense variant in one of the genes residing in this interval, C2ORF71, has recently been reported to be associated with RP. C2ORF71, encoding a putative protein of 1,288 amino acids, was found to be specifically expressed in human retina. Furthermore, RT-PCR analysis revealed that in the mouse eye, C2orf71 is expressed as early as embryonic day 14. Mutation analysis detected a 1 bp deletion (c.946 del; p.Asn237MetfsX5) segregating with RP in the Dutch family, whereas a nonsense mutation (c.556C > T; p.Gln186X) was identified in the Israeli family. Microsatellite-marker analysis in additional Israeli families revealed cosegregation of a C2ORF71-linked haplotype in one other family, in which a 13 bp deletion (c.2756_2768 del; p.Lys919ThrfsX) was identified. Clinically, patients with mutations in C2ORF71 show signs of typical RP; these signs include poor night vision and peripheral field loss, typical retinal bone-spicule-type pigment deposits, pale appearance of the optic disk, and markedly reduced or completely extinguished electroretinograms. In conclusion, truncating mutations in C2ORF71 were identified in three unrelated families, thereby confirming the involvement of this gene in the etiology of arRP.

Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial.

OBJECTIVE: To explore the safety and efficacy of CF101, an A(3) adenosine receptor agonist, in patients with moderate to severe dry eye syndrome. DESIGN: Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study. PARTICIPANTS: Sixty-eight patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group. INTERVENTION: Patients were treated orally with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week posttreatment observation. MAIN OUTCOME MEASURES: An improvement of more than 25% over baseline at week 12 in one of the following parameters: (1) tear break-up time (BUT); (2) superficial punctate keratitis assessed by fluorescein staining results; and (3) Schirmer tear test 1 results. Clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements, and monitoring of adverse events. RESULTS: A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group. CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group. CONCLUSIONS: CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate to severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study of the drug as a potential treatment for the signs and symptoms of dry eye syndrome. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

In vitro simulation of the first technique for non-invasive measurement of volumetric ophthalmic artery blood flow in humans.

BACKGROUND AND OBJECTIVE: To evaluate the accuracy, reproducibility, and variability of volumetric flow measurements taken by color Doppler imaging ultrasound, using an in vitro "phantom" model to simulate the ophthalmic artery. MATERIALS AND METHODS: An agar flow phantom with two wall-less lumens was constructed to simulate the ophthalmic artery. Velocity and volumetric flow measurements were taken for various flow rates and ultrasound probe positions. The measurements were analyzed for accuracy, reproducibility, and variability. RESULTS: Velocity measurements were more accurate than flow measurements (8 of 24 vs 3 of 24 accurate trials). The average coefficient of variation for volumetric blood flow was 11.4% (n = 120). Volumetric flow significantly correlated with velocity (R(2) = 0.408, n = 600, P < .001). The highest correlation was achieved using the large lumen with the probe held at 75 degrees , offset to the flow (R(2) = 0.862, n = 75). CONCLUSION: Based on an in vitro model, non-invasive color Doppler imaging recordings of volumetric flow measurements in the ophthalmic artery significantly correlated with velocity and higher correlations were found using the larger lumens, although the data showed a lack of high accuracy in measurements of flow and velocity.

Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping.

Retinitis pigmentosa is the most common form of hereditary retinal degeneration, with a worldwide prevalence of 1 in 4,000. At least 28 genes and loci have been implicated in nonsyndromic autosomal recessive retinitis pigmentosa. Here we report two extended and highly consanguineous families segregating early onset retinitis pigmentosa. Despite the consanguinity in both families, we found allelic heterogeneity in one of them, in which affected individuals were compound heterozygotes for two different mutations of the CRB1 gene. In the second family we found evidence for locus heterogeneity. A novel homozygous mutation of RDH12 was found in only 14 of 17 affected individuals in this family. Our data indicate that in the other affected individuals the disease is caused by a different gene/s. These findings demonstrate that while homozygosity mapping is an efficient tool for identification of the underlying mutated genes in inbred families, both locus and allelic heterogeneity may occur even within the same consanguineous family. These observations should be taken into account, especially when studying common and heterogeneous recessive genetic conditions.

Vision screening among northern Israeli Jewish and Arab schoolchildren.

BACKGROUND: Uncorrected refractive error is the leading cause of visual impairment in children. In 2002 a screening project was launched in Israel to provide data on the effectiveness of the illiterate E-chart in identifying Jewish and Arab schoolchildren in need of a comprehensive eye examination. OBJECTIVES: To present the aims, design and initial results of the visual screening project and the prevalence of vision abnormality in the study population. METHODS: A cross-sectional population-based study was conducted during 2002-2003 among first- and eighth-graders in 70 schools in northern Israel. The nurse's test included use of the illiterate E-chart to measure visual acuity. The medical examination included vision history, clinical eye examination, VA and retinoscopy. The ophthalmologist's evaluation as to whether a child needed a referral for, diagnostic procedures, treatment and/or follow-up was recorded and compared with explicit referral criteria formulated after data collection. RESULTS: Of 1975 schoolchildren, 31% had abnormal VA, defined as VA worse than 6/6 in at least one eye, and a quarter had VA equal or worse than 6/12 in both eyes. The prevalence of vision abnormality among the children was 22.4% when based on the evaluation of the field ophthalmologist and 26.1% when based on two sets of explicit severity scores and referral criteria. CONCLUSIONS: Vision abnormality is a significant health problem among northern Israeli schoolchildren. This project is unique in scope and importance, providing evidence to assist policy making with regard to vision screening for schoolchildren (including data on test reliability and validity) and optimal VA cutoff level, and confirming the need for clinical guidelines regarding referral criteria.

The effect of latanoprost on ocular blood flow.

PURPOSE: To investigate the effect of latanoprost on ocular hemodynamics in healthy subjects. METHODS: In a randomized, double-masked, placebo-controlled crossover study, 12 healthy subjects received either placebo or latanoprost for 4 weeks in one randomly chosen eye. Following a 4-week washout period, each patient received the opposite treatment. Blood pressure, heart rate, logMar visual acuity, contrast sensitivity, iris photography, intraocular pressure (IOP), Heidelberg retinal flowmetry, and color Doppler imaging measurements were taken at baseline and post-treatment. Heidelberg retinal flowmetry images were analyzed using the pixel-by-pixel analysis. Color Doppler imaging measurements included peak systolic velocity and end diastolic velocities (cm/s), and the calculated resistance index. Pre- and post-treatment values were compared by Wilcoxon signed rank tests (P < 0.05 was considered to be statistically significant). RESULTS: There were no significant changes in heart rate, blood pressure, contrast sensitivity, or visual acuity with either treatment. Latanoprost demonstrated a significant reduction in both IOP (P = 0.005) and retinal blood flow at the 10th (P = 0.009) and 25th (P = 0.009) percentiles of Heidelberg retinal flowmetry measurements in the superior temporal region. Latanoprost, however, did not reduce blood flow in the inferior temporal region and did not significantly elevate the percentage of zero-flow pixels of the temporal peripapillary area. CONCLUSION: Latanoprost has mostly neutral effects on ocular circulation. These findings must be investigated in glaucoma patients who may respond differently than healthy subjects due to faulty vascular autoregulation.

[Ophthalmology in the Holy Land].

In this article the authors review the history of ophthalmology in the Holy Land in the era spanning from 1948 till nowadays. Although there is material concerning ophthalmology in the Holy Land, it is not well organized. Therefore, the authors considered it of utmost importance to gather all the material that exists regarding ophthalmology in the Holy Land. In this review the authors strived to present a view of ophthalmology in the Holy Land in its first steps. Moreover, the authors presented the latest developments in eye health care in local eye departments.

A novel splice-site mutation of TULP1 underlies severe early-onset retinitis pigmentosa in a consanguineous Israeli Muslim Arab family.

PURPOSE: To investigate the genetic basis for autosomal recessive severe early-onset retinitis pigmentosa (RP) in a consanguineous Israeli Muslim Arab family. METHODS: Haplotype analysis for all known genes underlying autosomal recessive RP was performed. Mutation screening of the underlying gene was done by direct sequencing. An in vitro splicing assay was used to evaluate the effect of the identified mutation on splicing. RESULTS: Haplotype analysis indicated linkage to the Tubby-like protein 1 (TULP)1 gene. Direct sequencing revealed a homozygous single base insertion, c.1495+2_1495+3insT, located in the conserved donor splice-site of intron 14. This mutation co-segregated with the disease, and was not detected in 114 unrelated Israeli Muslim Arab controls. We used an in vitro splicing assay to demonstrate that this mutation leads to incorrect splicing. CONCLUSIONS: To date, 22 distinct pathogenic mutations of TULP1 have been reported in patients with early-onset RP or Leber congenital amaurosis. Here we report a novel splice-site mutation of TULP1, c.1495+2_1495+3insT, underlying autosomal recessive early-onset RP in a consanguineous Israeli Muslim Arab family. This report expands the spectrum of pathogenic mutations of the TULP1 gene.

Performance measures of the illiterate E-chart vision-screening test used in Northern District Israeli school children.

OBJECTIVES: To evaluate the screening performance of 6/6 and 6/12 vision cut-offs with an illiterate E-chart implemented by a public health nurse to test children for ocular abnormalities and uncorrected refractive error. The gold standard diagnosis is an eye examination performed by an ophthalmologist. SETTING: A cross-sectional population-based study was conducted among 2113 students' ages 6-7 and 13-14 years old in 70 Northern District Israeli schools. METHODS: Students were tested by nurses and ophthalmologists. A nurse examination was carried out using the illiterate E-chart for vision measurement. The medical examination included vision history, clinical eye examination, vision and retinoscopy testing. The Physician's evaluation of whether students needed a referral for diagnostic procedures, treatment and/or follow-up was recorded. Screening test's performance was determined using ophthalmologist's decision regarding referral as the gold standard. Detection rate (DR), false-positive rate (FPR), odds affected positive result (OAPR), positive predictive value (PPV) and negative predictive value (NPV) were estimated overall and by students' demographic characteristics. RESULTS: For vision >6/6 cut-off in at least one eye (eyes tested separately): DR - 71.9% (95% CI 65.8-78.7%), FPR - 22.8% (95% CI 17.9-28.9%), OAPR - 0.98:1 (95% CI 0.84:1-1.15:1), PPV - 52.7% (95% CI 45.4-61.2%), NPV - 90.9% (95% CI 88.7-93.1%). For 6/12 vision cut-off, namely vision 6/12 or worse in both eyes (tested separately): DR - 58.6 (95% CI 51.8-66.4%), FPR - 15.2% (95% CI 10.9-21.1%), OAPR - 1.13:1 (95% CI 0.94:1-1.35:1), PPV - 61.1% (95% CI 52.9-70.6%), NPV - 87.6% (95% CI 84.9-90.4%). CONCLUSIONS: Vision-screening test performance measures are mild. It is suggested to change vision cut-off level that denotes vision abnormality from current policy of vision not equal 6/6 in both eyes (tested separately) to vision 6/12 or worse in both eyes (tested separately). This change will result in reduction of FPR from 22% to 15%, concomitant with an increase in false-negative rate from 28% to 41%. Students may be equally screened by either a senior or a less experienced nurse.

Dye dependent differences in arteriovenous passage times: a comparison of indocyanine green and fluorescein sodium dye analysis.

BACKGROUND AND OBJECTIVE: To evaluate the difference in arteriovenous passage time calculated from retinal angiograms using indocyanine green and fluorescein sodium dye in healthy individuals. PATIENTS AND METHODS: Examinations of eight healthy individuals (mean age +/- standard deviation: 27.3 +/- 4.2 years) who had four consecutive ophthalmic visits that were 2 weeks apart were analyzed. Indocyanine green and fluorescein angiography were performed sequentially (with the indocyanine green angiography occurring first) using scanning laser ophthalmoscopy. Arteriovenous passage times were calculated offline using digital angiogram video analysis. RESULTS: Mean arteriovenous passage times calculated from indocyanine green angiography (1.417 +/- 0.136 seconds) recordings were significantly shorter than fluorescein sodium times (2.539 +/- 0.421 seconds) (P < .0001) and intra-group variability was similar. There were no significant correlations between indocyanine green and fluorescein sodium arteriovenous passage times. CONCLUSION: Arteriovenous passage times calculated using indocyanine green and fluorescein angiography are not interchangeable.

[Ophthalmology in the Middle East from antiquity to the twentieth century].

This article reviews the history of ophthalmology in the Middle East in the era spanning from antiquity to the twentieth century. Although there is little material concerning ophthalmology in antiquity the authors strove to present the way people and healers overcome eye problems. Moreover, ophthalmology in middle ages was reviewed, with emphasis on the great role Arab and Muslim ophthalmologists had in developing eye care and ocular sciences. Finally, the latest developments in eye health care in our region were shown.

A common founder mutation of CERKL underlies autosomal recessive retinal degeneration with early macular involvement among Yemenite Jews.

PURPOSE: To investigate the genetic basis and clinical manifestations of a characteristic form of retinal degeneration in the Yemenite Jewish population. METHODS: Haplotype analysis for all known genes and loci underlying autosomal recessive nonsyndromic retinal degeneration was performed in a Yemenite Jewish family segregating autosomal recessive severe retinal degeneration. The causative mutation was detected by direct sequencing of the underlying gene, and its prevalence in additional affected and unaffected Yemenite Jews was determined. Patients who were homozygous for this mutation underwent ophthalmic evaluation, including funduscopy, electroretinography, electro-oculography, perimetry, and color vision testing. RESULTS: In the studied Yemenite Jewish family, we found evidence for linkage to the CERKL gene. Direct sequencing revealed a novel homozygous splice-site mutation, c.238+1G>A. An in vitro splicing assay demonstrated that this mutation leads to incorrect splicing. c.238+1G>A was found to cause retinal degeneration in six additional Yemenite Jewish families. The carrier frequency of this mutation in the Yemenite Jewish population is 4.4%. All c.238+1G>A homozygotes manifest widespread progressive impairment of rod and cone function with early macular involvement. CONCLUSIONS: c.238+1G>A is the second reported mutation of CERKL and is a prevalent founder mutation that underlies approximately 33% of autosomal recessive retinal degeneration cases in the Yemenite Jewish population. It is associated with a characteristic retinal degeneration phenotype with early macular involvement, concomitant progression of rod and cone impairment, and characteristic fundus findings. The identification of this mutation and phenotype will facilitate molecular diagnosis, carrier screening, and genetic counseling in the Yemenite Jewish population.

Laser ablation in eyes with congenital nystagmus.

PURPOSE: To report photorefractive keratectomy and LASIK for the correction of myopia in eyes with congenital nystagmus. METHODS: Photorefractive keratectomy was performed in one eye and LASIK performed in eight eyes of five adult patients (three men and two women) with congenital nystagmus. Mean patient age was 34 years. RESULTS: Preoperative refraction ranged between -1.50 and -22.00 diopters (D) sphere, and -0.50 and -3.25 D of astigmatism; best spectacle-corrected visual acuity (BSCVA) ranged between 2 m finger counting and 20/30. In all nine eyes, postoperative uncorrected visual acuity (UCVA) equaled or exceeded preoperative BSCVA. Postoperative topography showed central ablations. Results were stable at follow-up 18 months after surgery, except in one eye with follow-up of 4 months. Enhancement was not required in any eye. CONCLUSIONS: Positive results were achieved for ablation performed with a broad beam laser in eyes with nystagmus.

Pulsatile ocular blood flow: relationship with flow velocities in vessels supplying the retina and choroid.

BACKGROUND: Although ocular tonography measures a pulsatile component of the ocular perfusion, the retinal and/or choroidal components of this pulsatile flow remain undefined. AIM: To compare ocular tonography with the assessment of flow velocities in arteries supplying the retina, choroid and entire orbit. METHODS: 22 normal eyes from 11 subjects were studied. Pulsatile ocular blood flow (POBF) was measured using the ocular blood flow tonograph, and flow velocities in the ophthalmic, central retinal (CRA) and temporal short posterior ciliary arteries (TSPCA) using colour Doppler imaging. The correlation between POBF and retrobulbar flow velocities was determined. RESULTS: POBF correlated significantly with peak systolic velocity (PSV) of the CRA (r = 0.56, p = 0.007) and the TSPCA (r = 0.48, p = 0.02), and with the resistive index of the TSPCA (r = 0.45, p = 0.04). Additionally, pulse amplitude (PSV-end diastolic velocity) in the CRA and the TSPCA correlated significantly with POBF measurements (each p<0.05). However, POBF did not correlate with any flow velocity indices in the ophthalmic artery. CONCLUSION: POBF is associated with systolic and pulsatile components of blood flow velocities in both the CRA and the TSPCA. This result suggests that POBF determinations are influenced by the pulsatile components of both choroidal and retinal perfusion.

Relationship of cerebral blood flow and central visual function in primary open-angle glaucoma.

PURPOSE: To investigate the relations between middle cerebral artery (MCA) blood flow velocities and central visual function measured by foveal cone electroretinograms (ERG) and visual field. METHODS: Fifteen primary open-angle glaucoma patients were recruited. The eye with the more severe visual field defect (full threshold 24-2) and/or optic disc damage was chosen. Measurements included brachial arterial pressure, heart rate, visual acuity (logMAR), contrast sensitivity (CSV-1000), central visual field (Humphrey SITA 10-2), foveal cone ERG, and transcranial Doppler. Pearson correlation coefficients were estimated to assess the strength of the linear relationship between the MCA flow velocity and the other measured parameters. RESULTS: Visual field was successfully completed in 12 eyes. We were unable to obtain ERG responses and MCA velocity readings for 1 patient. A significant correlation was observed between MCA mean flow velocity and focal cone ERG amplitude [r=0.69, n=13, confidence interval (CI) 0.22, 0.90, P=0.009], but correlation between mean foveal cone ERG implicit time and middle cerebral was not statistically significant (r=0.011, n=13, CI 0.47, 0.63). A significant correlation was also observed between MCA mean flow velocity and mean sensitivity (r=0.76, n=12, CI 0.32, 0.93, P=0.005), and mean defect (r=0.73, n=12, CI 0.28, 0.92, P=0.007) of the central visual field, logMAR visual acuity (r=0.57, n=14, CI 0.05, 0.84, P=0.036), and contrast sensitivity (r=0.61, n=13, CI 0.09, 0.87, P=0.027). CONCLUSIONS: Our findings suggest that in certain primary open-angle glaucoma patients diminished central visual function may be one manifestation of widespread cerebrovascular insufficiency.

Reactivation of ocular toxoplasmosis after LASIK.

PURPOSE: To report a reactivation of ocular toxoplasmosis after LASIK. METHODS: Case report of a 34-year-old man who underwent bilateral LASIK. The posterior segment examination revealed an old toxoplasmosis scar in the retinal periphery of the right eye. RESULTS: Uncorrected visual acuity improved postoperatively, and the patient was satisfied. However, 52 days after the procedure, he complained of loss of visual acuity in his right eye. Examination revealed signs of anterior uveitis, vitreitis, and active chorioretinal lesion satellite of the old toxoplasmosis scar. The patient was treated with a multidrug regiment with resolution of the vitreous and lesion activity. CONCLUSIONS: Toxoplasmosis reactivation may develop after LASIK.

Management of pellucid marginal degeneration with intracorneal ring segments.

PURPOSE: To present intracorneal ring segments for potential management of pellucid marginal degeneration. METHODS: A 41-year-old man with pellucid marginal degeneration with poor visual acuity due to irregular astigmatism was treated with Intacs microthin insert (KeraVision, Fremont, Calif) in the left eye. RESULTS: Uncorrected visual acuity improved from 2/60 to 6/60 following the procedure. The procedure completely eliminated myopia of -8.00 diopters and improved the irregularity of the astigmatism, although it did not change its magnitude. CONCLUSIONS: Insertion of the intracorneal ring segment improves visual acuity in pellucid marginal degeneration by flattening the central corneal protrusion, thus reducing myopia and improving the astigmatism irregularity.

A nonsense mutation in the glucosaminyl (N-acetyl) transferase 2 gene (GCNT2): association with autosomal recessive congenital cataracts.

PURPOSE: To identify the genetic defect associated with autosomal recessive congenital cataract in four Arab families from Israel. METHODS: Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point lod scores were calculated using MLINK of the LINKAGE program package. Mutation analysis of the glucosaminyl (N-acetyl) transferase 2 gene (GCNT2) gene was performed by direct sequencing of PCR-amplified exons. RESULTS: The cataract locus was mapped to a 13.0-cM interval between D6S470 and D6S289 on Chr. 6p24. A maximum two-point lod score of 8.75 at theta = 0.019 was obtained with marker D6S470. Sequencing exons of the GCNT2 gene, mutations of which have been associated with cataracts and the i blood group phenotype, revealed in these families a homozygous G-->A substitution in base 58 of exon-2, resulting in the formation of premature stop codons W328X, W326X, and W328X, of the GCNT2A, -B, and -C isoforms, respectively. Subsequent blood typing of affected family members confirmed the possession of the rare adult i blood group phenotype. CONCLUSIONS: A nonsense mutation in the GCNT2 gene isoforms is associated with autosomal recessive congenital cataract in four distantly related Arab families from Israel. These findings provide further insight into the dual role of the I-branching GCNT2 gene in the lens and in reticulocytes.

Choroidal perfusion perturbations in non-neovascular age related macular degeneration.

AIM: Choroidal perfusion, affected in age related macular degeneration (AMD), is difficult to objectively assess given the overlying retinal circulation. This study more objectively compared choroidal perfusion parameters in a group with non-neovascular AMD to an unaffected age matched control group. METHODS: 21 non-neovascular AMD subjects and 21 age matched control subjects without evidence of AMD underwent assessment of their choroidal blood flow in a case-control study. Scanning laser ophthalmoscope indocyanine green (ICG) angiograms were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary retina were evaluated by producing a graph of intensity of fluorescence of each area over time. The mean of the filling times and the heterogeneity of the filling times were assessed. RESULTS: The means of the filling times within the perifoveal regions and the hetereogeneity of the filling times between regions within the same eyes were significantly greater in the AMD patients compared with the control subjects. CONCLUSIONS: Delayed and heterogeneous filling of the choroid was objectively demonstrated in eyes with non-neovascular AMD compared with age matched controls without evidence of AMD, using an area dilution analysis technique applied to ICG angiography.

Keratitis after implantation of intrastromal corneal ring segments.

A 53-year-old man had implantation of 2 intrastromal corneal ring segments (Intacs, Addition Technology Inc.) in the left eye. Several days after the lower segment was exchanged, an infiltrate was present at the corneal incision site. This progressed to a lower channel infection followed by diffuse keratitis. Culture from the conjunctiva was positive for Staphylococcus epidermidis, but cultures from the cornea were negative for microorganisms. Later, 2 gas bubbles appeared at the interface. The patient was treated with topical and subconjunctival antibiotics and channel irrigation. The keratitis resolved, leaving a neovascularized opacity at the nasal part of the lower channel.