Special considerations in low-tension glaucoma

Low-pressure (low-tension) glaucoma is reviewed in relation to neuroprotection, that is, the therapeutic strategy to keep neurons living and functionally connected to targets within the brain. Baseline results of the Low-Pressure Glaucoma Treatment Study (LoGTS) are reviewed.     

Genetic heterogeneity in Hispanic families with autosomal dominant juvenile glaucoma

A gene for autosomal dominant, juvenile-onset, primary open angle glaucoma (glcia) has been previously mapped to Iq21-31 in several Caucasian pedigrees. We studied two Hispanic families with this disease to determine if their disease genes also map to this region. Individuals were considered as being affected if they had iop > 30 mmHg (without treatment) and glaucomatous optic nerve damage or visual field defects. Persons older than 40 years with intraocular pressures 21 mmHg and no evidence of optic nerve damage or visual field loss were scored as unaffected. Individuals not falling into these two categories were considered unknown. Genomic dna was extracted from blood samples and subjected to PCR-based microsatellite marker analysis. Computer-based linkage analysis was used to determine if the disease gene mapped to chromosome Iq21-31. In the family from the Canary Islands, the disease gene was linked to the chromosome Iq21-31 region previously identified by other researchers. Markers D1S212 and D1S218 produced maximum lod scores of 3·38 and 2.99, respectively. In the family from the Balearic Islands, the disease gene was excluded from this region by genetic linkage analysis. Haplotype analysis also excluded the disease gene from chromosome Iq21-31. Our Hispanic families showed genetic heterogeneity with respect to autosomal dominant, juvenile-onset, primary open angle glaucoma.     

Optic disc hemorrhage in low-tension glaucoma

The prevalence of optic disc hemorrhage (DH) was determined in groups consisting of 192 primary open-angle glaucoma, 113 primary angle-closure glaucoma, 78 low-tension glaucoma, and 473 normal patients. The DH was mot prevalent (20.5%) among low tension glaucoma patients (chi 2; P less than 0.001). The epidemiological features of DH were studied in 58 low-tension glaucoma patients by examining them every one to four weeks from 6 to 32 months. All the DHs but one took place within a seven-month follow-up and the incidence of DH varies from 0 to 10% during the 32-month follow-up period. The overall incidence of DH was 24.8% during that period of time. Recurrences were seen in 64% of the eyes and 92% of these occurred within 28 weeks following the previous hemorrhages. Ninety-two percent of all DHs were present for at least four weeks. Low-tension glaucoma eyes seem to consist of two different groups; one which develops recurrent DH and one which is very unlikely to bleed through its entire course.     

Central corneal thickness in low-tension glaucoma

BACKGROUND: It is possible that the intraocular pressure (IOP) is underestimated in eyes whose central cornea is thinner than normal. The objective of this study was to determine and establish the significance of central corneal thickness in patients with low-tension (normal-tension) glaucoma compared with those with chronic open-angle glaucoma (COAG) or ocular hypertension and healthy eyes. METHODS: The study was carried out from February 1998 to May 1999. Central corneal thickness was measured by ultrasonic pachymetry and IOP was measured by Goldmann applanation tonometry in 25 patients with low-tension glaucoma (untreated IOP less than 21 mm Hg with evidence of optic nerve head damage and corresponding visual field loss on automated perimetry), 80 patients with COAG (untreated IOP 21 mm Hg or greater with evidence of optic nerve head damage and corresponding visual field loss on automated perimetry), 16 patients with ocular hypertension (untreated IOP 21 mm Hg or greater, with normal optic nerve head and no history of glaucoma or elevated IOP, and normal visual field on automated perimetry) and 50 control subjects (untreated IOP less than 21 mm Hg with normal optic nerve head and no history of glaucoma or elevated IOP). Analysis with Pearson's product-moment correlation was performed to determine the correlation of IOP and central corneal thickness, and one-way analysis of variance was used to compare corneal thickness between groups. RESULTS: The central cornea was significantly thinner in the low-tension glaucoma group (mean 513.2 mu [standard deviation (SD) 26.1 mu]) than in the COAG group (mean 548.2 mu [SD 35.0 mu]) and the control group (mean 556.7 mu [SD 35.9 mu]) (p < 0.001). No significant difference in corneal thickness was found between the COAG and control groups. The ocular hypertension group had significantly thicker corneas (mean 597.5 mu [SD 23.6 mu]) than the three other groups (p < 0.001). INTERPRETATION: Patients with low-tension glaucoma may have thinner corneas than patients with COAG and healthy subjects. This results in underestimation of their IOP. Corneal thickness should be taken into account when managing these patients to avoid undertreatment.     

Congenital glaucoma of dominant autosomal transmission apropos of a family. Management

The study of three consecutive generations of patients having a late revelation congenital glaucoma, make us discuss about several kinds of inheritance of the congenital glaucoma, especially the dominant autosomal form, well adapted to a genetic counsel which is necessary in all the cases, because of the severity of this disease.     

The neurologic evaluation of patients with low-tension glaucoma

One hypothesized cause of low-tension glaucoma is chronic or intermittent ischemia of the optic nerve. Since the optic nerve and brain are both parts of the central nervous system and share a common blood supply, the authors wondered if patients with low-tension glaucoma might also have clinical or radiographic evidence of cerebral atrophy. In this study, 27 patients with low-tension glaucoma were examined using neurobehavioral testing, electroencephalography, computerized tomographic scan, neurological history, and physical examination. In only a small number of patients were these tests abnormal. However, 12 of the 27 patients gave a history of common or classic migraine. This unexpected finding raises the possibility that migraine-related ischemia might be the pathogenic mechanism in some cases of low-tension glaucoma.     

Argon laser trabeculoplasty in progressive low-tension glaucoma

Twenty-two phakic eyes with progressive low-tension glaucoma had a 360-degree argon laser trabeculoplasty (ALT). Seven of these eyes had diurnal curves performed pre- and two months postlaser treatment to measure the effect of ALT on diurnal pressure variation. Sixteen of the 22 eyes (73%) were clinical successes with a 4.9 mm Hg decrease at 12 months in the successful group. However there was a decreasing pressure lowering effect with time with a mean follow-up of 21.6 months. The diurnal curve data showed a 6.2 mm Hg decrease between the mean pressure pretreatment and two months postlaser treatment. The mean peak pressure posttreatment was 13.29 mm Hg, a 6.17 mm Hg decrease from the prelaser mean peak pressure. The finding of 24-hour pressure control and a reduction in the mean peak pressure confirms the usefulness of ALT in progressive low-tension glaucoma and we recommend that it be utilized as the step in between maximally tolerated medical therapy and filtering surgery.     

青光眼滤过术后低眼压性浅前房原因探讨

目的 分析青光眼滤过术后发生低眼压性浅前房的原因,以减少浅前房的发生。方法 292例(345只跟)青光眼行小梁切除和虹膜根切术,对其病历进行回顾性分析。结果 (1)发生浅前房共69只眼(20％),其中低眼压性浅前房65只眼(94．2％)；(2)在低眼压性浅前房病例中，眼压≤5mmlHg者60只眼(92．3％)．眼压在5～10mmHg者5只眼(7．7％)：(3)在低眼压性浅前房中脉络膜脱离者48只眼(73．8％),其它原因17只眼(26．2％)；(4)在低眼压性浅前房病历中．术前房角开放≤窄Ⅱ者46只眼(70．8％),≥窄Ⅲ者19只眼(29．2％)。结论 高滤过、低眼压房水动力学改变是低眼压性浅前房形成最初的基本原因．而脉络膜脱离则是低眼压性浅前房形成最主要原因。     

Possible significance of cilioretinal arteries in low-tension glaucoma

Cilioretinal arteries arise from the short posterior ciliary artery circulation or directly from the choroidal circulation. The presence of a cilioretinal artery may in compromised discs steal flow from the peripapillary circulation and account for worsening glaucoma damage. We reviewed the records of 33 patients with unilateral cilioretinal arteries admitted for investigation of low-tension glaucoma. We looked for absolute difference between the affected and unaffected eyes as well as percent difference relative to the mean value for the two eyes and to the value for the unaffected eye in the following variables: mean defect, corrected loss variance or corrected pattern standard deviation, and adjusted neuroretinal rim area. No statistically significant differences were found. The mean disc area for the eyes with cilioretinal arteries was significantly larger than that previously reported for normal eyes. The results suggest that if vascular steal exists because of the presence of this artery, it is not of major clinical importance.     

Incomplete penetrance of CRX gene for autosomal dominant form of cone-rod dystrophy

Purpose: Cone-rod dystrophy (CRD) is an inherited retinal dystrophy that is transmitted via different modes of inheritance. Mutations in more than 30 genes have been identified to cause the disease. We aimed to investigate the genetic agents of two unrelated cone-rod dystrophy affected Iranian families with autosomal recessive inheritance patterns.

Methods: Whole-exome sequencing (WES) was performed for identification of the disease-causing mutations in the probands of both families. The candidate mutations were further confirmed by Sanger sequencing. Samples from five available members of each family were then sequenced for the mutations present in the probands. Comprehensive ocular examinations for all members of the families carrying the mutations were completed by ophthalmologists.

Results: We identified a novel premature stop codon c.310C>T in CRX gene in heterozygote form in two symptomatic and two non-symptomatic members of one family (family-A), and a known CRX mutation c.122G>A in homozygote form in another (family B). c.122G>A has been reported to cause late-onset autosomal dominant form of the disease in previous studies. However, the middle-aged heterozygous carriers of the mutation in this family showed normal phenotype.

Conclusion: The CRX gene has been previously linked to the autosomal dominant form of cone-rod dystrophy. We report incomplete penetrance of CRX gene for autosomal dominant form of the disease. Incomplete penetrance of the mutations may be partly caused by the influence of other genes in the complex genetic network underlying retinal regulation.     

Genetic mapping of autosomal dominant primary open-angle glaucoma (POAG) in Sardinia

Primary open-angle glaucoma (POAG) can be subdivided into two groups according to age of onset: (1) the more prevalent middle to late-age-onset chronic open-angle glaucoma (COAG) diagnosed after age 40, and (2) the less common form, juvenile open-angle glaucoma (JOAG), which occurs between 3 years of age and early adulthood. Susceptibility to either COAG or JOAG has been found to be inherited. The discovery of several genetic markers spanning the region 1q21-q24 in genetic linkage with autosomal dominant juvenile open-angle glaucoma (adJOAG) represents a major breakthrough towards the localisation of gene(s) responsible for the disease. Linkage analysis is a powerful means of distinguishing disease loci in large families with dominant disease. However the size of the group of families may represent a crucial factor for the linkage analysis. Sardinia is an island with a relatively isolated ethnic group showing a relatively high frequency of ad JOAG and COAG (Fossarello et al., 1994) and it is genetically more homogeneous than most Western populations. Therefore it represents an ideal ethnic group to search for linkage. We identified 18 families affected by POAG in which the disease appears to be inherited as autosomic dominant trait. In all families but two, occurrence of both JOAG and COAG in the same kindred was observed. Identification of adPOAG locus was performed by linkage analysis using 9 microsatellite markers spanning the region 1q21-q24. No significant linkage was observed. Our findings provide further evidence for genetic heterogeneity in autosomal dominant primary open angle glaucoma, even in a geographic area where a relatively homogeneous genetic background exists.     

True tolerant intraocular pressure in glaucoma, ocular hypertension and low-tension glaucoma

Measurements of the true tolerant intraocular pressure (IOP) in 500 eyes of 384 patients with primary glaucoma and in 26 eyes of 13 patients with ophthalmic hypertension have demonstrated that the value of the true tolerant 10P is close to the lowest border of the mean statistical range of normal ophthalmic tone values, this value being, on an average, 13.4 mm Hg in primary glaucoma and 10.2 mm Hg in low-pressure glaucoma, whereas in ophthalmic hypertension it has been much higher - 24.8 mm Hg. The intolerance index in stabilized glaucoma does not surpass 4 mm Hg with both the true and the tonometric 10P.     

Investigations into a vascular etiology for low-tension glaucoma

Increased intraocular pressure is accepted as a primary etiologic factor for the atrophy of the optic nerve head and visual field defects of high-tension glaucoma. Other factors must be present to explain these findings in low-tension glaucoma. One of the current theories is that low-tension glaucoma is the result of decreased optic nerve perfusion on the basis of vascular disease or other factors such as altered blood viscosity. This study compared the non-invasive vascular profiles, coagulation tests, and rheological profiles of 46 consecutive cases of low-tension glaucoma with 69 similarly unselected cases of high-tension glaucoma and 47 age-matched controls. Despite the multifactorial approach and the use of previously validated objective tests, no significant group differences were detected with any of the above investigations. If vascular disease is important in the etiology of low-tension glaucoma, then it must be localized or vasospastic since this study does not support the concept of a generalized vascular etiology, either of an atheromatous or hyperviscous nature, for the genesis of low-tension glaucoma.     

Systemic factors in patients with low-tension glaucoma.

Nineteen patients (38 eyes) with low-tension glaucoma were compared with 53 subjects (106 eyes) with ocular hypertension. Comparable for age and sex, the 2 groups were assessed with respect to haematological and biochemical criteria, physical activity, and medical history. Statistical analyses of the differences between the 2 groups highlighted the importance of diastolic ophthalmodynamometry levels, prediagnosis exercise habits, cardiovascular disease status, and possibly systolic blood pressure. Patients with low-tension glaucoma suffered a higher prevalence of multiple abnormalities of these systemic factors than did their ocular hypertensive counterparts. There were no significant differences between the 2 groups with respect to the many other factors examined.     

小梁切除术后低眼压性浅前房原因探讨与诊治体会

目的:探讨青光眼小梁切除术后浅前房的原因,寻求有效的诊治方法。方法:回顾总结2003-06/2007-06间285例(303眼)抗青光眼小梁切除术及术后发生低眼压性浅前房的原因、程度及诊疗过程。结果:本组发生术后低眼压性浅前房58例89眼(29.4%)。其中,结膜切口漏6眼(6.7%),滤过过强46眼(51.6%)脉络膜、睫状体脱离37眼(41.6%。)结论:抗青光眼小梁切除术后低眼压性浅前房原因复杂,其中,除滤过过强外,脉络膜、睫状体脱离是很重要的一个原因。     

Fluorescein angiography in chronic simple and low-tension glaucoma.

Fluorescein angiograms were performed on a group of low-tension glaucoma and chronic simple glaucoma patients with similar extent of visual field loss, under standardised conditions, to see whether differences attributable to chronic intraocular pressure elevation could be detected. There was no evidence for difference in circulation times between these two groups. There was no evidence that hypoperfusion of the peripapillary choroid contributed to optic nerve hypoperfusion. Low-tension glaucoma patients demonstrated focal sector hypoperfusion of the optic nerve in every case, while the chronic simple glaucoma patients demonstrated a wide range of optic nerve fluorescence, suggesting both focal and diffuse optic nerve head hypoperfusion. It was concluded that, while focal hypoperfusion of the optic nerve may reflect susceptible vasculature at the nerve head with or without intraocular pressure elevation, diffuse hypoperfusion suggested that prolonged intraocular pressure elevation may simultaneously affect the whole of the optic nerve head. This could be a direct effect on blood vessels or a mechanical effect with secondary vascular changes.     

Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese.

We studied the prevalence of migraine in low-tension glaucoma (LTG) and primary open-angle glaucoma (POAG). Seventy seven Japanese patients with LTG, 73 with POAG, and 75 normal subjects were randomly selected and tested with a headache questionnaire. The prevalence of headache with or without typical migrainous features (unilateral headache or ocular pain, nausea, vomiting, and visual disturbance before headache) was 51% in LTG, 42% in POAG, and 44% in normal patients. The prevalence of headache with two migrainous features or more (probable migraine) was 17% in LTG, 11% in POAG, and 12% in normal subjects. The prevalence of headache with three migrainous features (classical migraine) was 5% in LTG, 3% in POAG, and 3% in normal subjects. There was no statistically significant difference in the prevalence of any types of migraine between the three groups of patients (p greater than 0.05). These results suggest there is no significant relationship between migraine and LTG or POAG in Japanese patients.