Mitochondrial abnormalities in patients with primary open-angle glaucoma

PURPOSE: Primary open-angle glaucoma (POAG) is the second most common cause of blindness. It has been linked to mutations in the myocilin (MYOC) and optineurin (OPTN) genes, although mutations have been found in <5% of patients. The pathologic mechanism(s) of POAG remain unknown but may include retinal ganglion cell apoptosis, which causes progressive damage to axons at the optic nerve head. METHODS: In 27 patients with definite POAG, the MYOC and OPTN genes were sequenced, the entire mitochondrial (mt)DNA coding region was sequenced, relative mtDNA content was investigated, and mitochondrial respiratory function was assessed. RESULTS: Only three benign polymorphisms were identified in MYOC and OPTN in patients with POAG and in control subjects. Conversely, 27 different novel nonsynonymous mtDNA changes were found, only in patients with POAG (not control subjects), 22 of which (found in 14 patients) were potentially pathogenic. Unlike Leber hereditary optic neuropathy, most mtDNA sequence alterations in patients with POAG were transversions-sequence changes that alter the purine/pyrimidine orientation and imply oxidative stress. mtDNA content was relatively increased in 17 patients with POAG compared with age-matched control subjects, also implying a possible response to oxidative stress. Mean mitochondrial respiratory activity was decreased by 21% in patients with glaucoma compared with control subjects (P<0.001). CONCLUSIONS: These results reveal a spectrum of mitochondrial abnormalities in patients with POAG, implicating oxidative stress and implying that mitochondria dysfunction may be a risk factor for POAG. This concept may open up new experimental and therapeutic opportunities.     

原发性开角型青光眼的系统性危险因素

眼压异常升高是原发性开角型青光眼最主要的危险因素。临床目前一直沿用以眼压为靶点的青光眼诊疗模式。近年来发现,循环血流、体质指数、颅内压、营养代谢、中医偏颇体质类型、某些系统性疾病等多种系统性危险因素可能与青光眼发生、发展和转归相关。纠正系统性危险因素能否延缓青光眼进展被日益关注,成为潜在的青光眼辅助诊疗靶点。本文对各类青光眼系统性危险因素进行介绍,倡导重视系统性危险因素,提出以系统危险因素评估和个性化眼体同治相结合的青光眼诊疗体系。（眼科,2022,31:325-329）     

Psychological characteristics of patients with primary open-angle glaucoma

Psychological disorders of different severity are observed in 89.7% patients with primary open-angle glaucoma. They can be detected both clinically and by psychological tests. The psychological status and personality characteristics of patients with glaucoma were evaluated by SMOL method and Cattel's 16 Personality Factors. Signs of psychological disadaptation are more pronounced in patients with the initial and well-developed stages of the disease and in those not treated surgically. The duration of the disease does not affect the psychological characteristics of patients with primary open-angle glaucoma. Consideration for the psychological factor is obligatory in combined therapy of patients with glaucoma.     

Apolipoprotein E polymorphisms in patients with primary open-angle glaucoma

PURPOSE: To investigate apolipoprotein E (APOE) polymorphisms, which are known to influence the risk of Alzheimer disease (AD), in patients with primary open-angle glaucoma (POAG). DESIGN: Retrospective case-control association study. METHODS: Patients with POAG (n = 242) and controls (n = 187) were analyzed for the APOE epsilon 2/epsilon 3/epsilon 4 polymorphisms using minisequencing technique. RESULTS: The Alzheimer-associated APOE epsilon 4 allele had similar frequencies in the POAG group and in the control group. There was no difference between cases and controls with regard to APOE genotypes. CONCLUSIONS: If a common pathogenic mechanism exists for the two age-related neurodegenerative diseases, POAG and AD, it does not involve APOE polymorphisms.     

Bradykinin sensitivity in primary open-angle glaucoma and normal-tension glaucoma patients

PURPOSE: To report the reaction after intradermal injection of bradykinin in nonglaucoma, primary open-angle glaucoma, and normal-tension glaucoma subjects. DESIGN: Prospective comparative study. METHODS: The study participants were 14 healthy control subjects, 16 patients with primary open-angle glaucoma, and 15 patients with normal-tension glaucoma. In each participant, the wheal response to intradermal injection of 10 microg bradykinin in the volar forearm was measured by a masked observer. RESULTS: There was no significant difference in the wheal response to bradykinin between control subjects and primary open-angle glaucoma patients (P =.73) and between primary open-angle glaucoma patients and normal-tension glaucoma patients (P =.09). However, there was a significant difference in the wheal response to bradykinin between control subjects and normal-tension glaucoma patients (P =.04). CONCLUSIONS: These in vivo structure-activity studies may suggest abnormalities of the tissue kallikrein-kinin system in normal-tension glaucoma.     

川芎嗪对原发性开角型青光眼患者的治疗作用

目的 探讨中药川芎嗪对原发性开角型青光眼的血液流变学、眼底荧光血管造影以及视功能的影响。方法 采有自身对照的方法对眼压已控制的原发性开角型青光眼患者１１例（１９）眼进行川芎嗪治疗前后血液流变学测定、眼底蓉光血管造影、Ｈrmphrey视野检查以及图形视诱发电位（ＰＶＥＰ）检测。结果 用磷酸川芎嗪治疗后患者血液流变学各指标明显下降（Ｐ＜０．０５～０．００１）;眼底荧光血管造影臂－脉络膜循环时间从隧的１４．６     

Methylenetetrahydrofolate reductase genetic polymorphisms in patients with primary open-angle glaucoma

PURPOSE: Hyperhomocysteinemia has been found in patients with primary open-angle glaucoma. The purpose of the present study was to determine if hyperhomocysteinemia-associated polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR) are overrepresented in primary open-angle glaucoma. METHODS: Patients with primary open-angle glaucoma (n = 243) and controls (n = 187) were analyzed for the MTHFR 677 C > T and 1298 A > C polymorphisms using minisequencing technique. RESULTS: No significant differences were observed in allele and genotype frequencies of the MTHFR 677C > T and 1298A > C polymorphisms between controls and the primary open-angle glaucoma group. CONCLUSIONS: If hyperhomocysteinemia is important in the pathogenesis of glaucoma, this study does not support a role for MTHFR polymorphisms in this context.     

Lifetime visual prognosis for patients with primary open-angle glaucoma

AIM: To investigate final visual outcome in primary open angle glaucoma (POAG) including low-tension glaucoma (LTG). METHODS: Retrospective review of case notes for patients who died between 1999 and 2002. All were booked for a follow-up appointment in glaucoma clinic at time of death. RESULTS: A total of 121 case notes were reviewed. In all, 113 patients had POAG and eight had LTG. All were White Caucasians. Mean ages at presentation and death were 74.6 (SD 9.6, range 49-94) and 81.9 (SD 8.3, range 51-98) years, respectively. Mean follow-up duration was 7.4 (SD 6.8, range up to 29) years. Average number of clinic visits was 18 (SD 17, range 1-95). At final visit, 50.4% had cataract operations, and 45.5% had glaucoma operations. At final visit, vision was inadequate for driving in the UK in 47.1%. In 18.2%, this was due to glaucoma alone, while in 28.9%, other ocular pathologies contributed to poor vision. In all, 14% were eligible for partial sight certification, with 6.6% due to glaucoma alone. A total of 3.3% were eligible for blind certification, none due to glaucoma alone. CONCLUSION: This study shows that POAG does affect the quality of life, with regards to glaucoma clinic visits, eye drops, and surgical procedures. Most patients with treated POAG in Norfolk will retain useful vision for their whole life. A significant proportion of patients with POAG do lose vision resulting in driving ineligibility and certification as visually impaired, although actual blindness is uncommon.     

Visual field defects in diabetic patients with primary open-angle glaucoma

We reviewed the automated visual field tests of 110 nondiabetic and 87 diabetic patients with primary open-angle glaucoma randomly selected from a large glaucoma practice to investigate a possible qualitative difference in the pattern of visual field defects between nondiabetic and diabetic patients with primary open-angle glaucoma. A single reviewer analyzed, in masked fashion, the visual field tests of each patient and decided whether or not visual field defects were present mainly in the inferior half of the visual field. Of the 110 nondiabetic patients, 40 (36.4%) had visual field defects located mainly in the inferior half of the visual field in one or both eyes, whereas 56 of the 87 (64.4%) diabetic patients had such defects. This difference was statistically significant (P = .0001). We believe that a vascular factor, such as that attributable to diabetes mellitus, may influence glaucomatous optic nerve damage, thus causing a difference in the pattern of visual field loss in patients with primary open-angle glaucoma.     

Aqueous humor erythropoietin levels in patients with primary open-angle glaucoma

PURPOSE: To evaluate the levels of erythropoietin (EPO) in the aqueous humor in eyes with primary open-angle glaucoma (POAG) and without glaucoma. METHODS: Levels of EPO were measured using a sandwich enzyme-linked immunosorbent assay kit in aqueous humor aspirates taken during anterior segment surgery from 45 patients, of whom 20 had POAG and 25 had senile cataract only. RESULTS: The mean aqueous humor EPO concentration in eyes with POAG (10.91+/-4.32 mU/mL) was significantly higher than that from eyes with cataract (8.24+/-1.77 mU/mL, P=0.008). There was no significant difference between the serum EPO concentrations of POAG (26.46+/-10.36 mU/mL) and the control group (24.50+/-7.59 mU/mL, P=0.468). There was no correlation (P=0.165) between the EPO aqueous humor concentration and the EPO serum concentration while there was no correlation between the EPO aqueous humor concentration and the EPO serum concentration in the control group (P=0.819). CONCLUSIONS: The aqueous humor EPO level is increased in eyes with POAG.     

Argon laser trabeculoplasty in younger patients with primary open-angle glaucoma

We conducted a retrospective comparison of the effectiveness of argon laser trabeculoplasty in controlling increased intraocular pressure in two different age groups treated for medically uncontrolled primary open-angle glaucoma. Of 15 eyes of patients less than 40 years old who had primary open-angle glaucoma, nine (60%) had uncontrolled intraocular pressures postoperatively and needed filtering surgery within two years of argon laser trabeculoplasty. Only two of 29 (7%) eyes in older patients had unacceptably high intraocular pressures during a mean (+/- 1 S.D.) follow-up period of 17 +/- 5 months. Older eyes had greater decreases in intraocular pressure (12 +/- 6 mm Hg) than younger eyes (5 +/- 6 mm Hg) after laser treatment. Failure in young eyes appeared to correlate with a high preoperative intraocular pressure. Thus, argon laser trabeculoplasty is not a reliably effective form of therapy for younger patients with primary open-angle glaucoma.     

Repeatability of primary selective laser trabeculoplasty in patients with primary open-angle glaucoma

To determine if primary selective laser trabeculoplasty (SLT) can be repeated with clinical benefit in patients with primary open-angle glaucoma (POAG). Forty-two eyes of 42 patients with POAG were studied. All patients underwent primary SLT treatment of 40–50 shots to the trabecular meshwork over 360°. The treatment response at the initial post-SLT visit (4 weeks), and second post-SLT visit (mean 4 months), clinical success and duration of clinical success were measured. SLT was repeated in all patients after failure to maintain target intraocular pressure (IOP). The same parameters were measured after repeat SLT. The main outcome measures were success of treatment (as defined by reduction of IOP by at least 20 % and below an individually determined target pressure), duration of treatment success and reduction in IOP. No significant difference between initial and repeat treatments was found for mean reduction in IOP or success rate, or duration of success. Survival analysis found significantly longer benefit for repeat treatment compared to initial treatment (P < 0.01). Repeat SLT treatment in eyes with POAG has similar efficacy to primary SLT treatment with respect to reduction in IOP and success rates, produces a longer duration of treatment success.     

Prevalence of normal-tension glaucoma and primary open-angle glaucoma in patients with collagen diseases

PURPOSE: To investigate the prevalence of normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG) in patients with collagen diseases and determine whether an immunocompromised condition is present in a subset of glaucoma patients. METHODS: Three glaucoma specialists prospectively examined patients with collagen diseases. The diagnostic process included applanation tonometry, slit-lamp examination, gonioscopy, direct ophthalmoscopy, and automated static perimetry. Twenty-four-hour intraocular pressure monitoring was done when necessary. Using the results of a population-based survey conducted in Japan, we calculated an expected number of cases of NTG and POAG, and compared these with the actual number of cases. RESULTS: Of the 153 patients with collagen diseases examined, we found 6 patients with NTG and 2 patients with POAG. Of these 8 patients, 2 with progressive systemic sclerosis (PSS), one with NTG, and the other, POAG, had a history of being on systemic steroidal therapy. The prevalence of NTG and POAG was significantly higher in women patients having collagen diseases as compared with normal women (P = .027). CONCLUSION: Women patients with collagen diseases are highly susceptible to NTG and POAG.     

Retinal mean transit time in patients with primary open-angle glaucoma and normal-tension glaucoma

PURPOSE: To compare the mean transit time (MTT) of retinal circulation in eyes with primary open-angle glaucoma (POAG) and eyes with normal-tension glaucoma (NTG) and examine the possible relationship between MTT and visual field damage, expressed as mean deviation (MD). METHODS: Video fluorescein angiography was performed in 40 patients with POAG or NTG. Dye curves for fluorescein passing through the retinal arteries and veins were used to calculate MTT in each patient with a computer-assisted technique based on an impulse-response analysis (MTT(IR)). RESULTS: We were able to analyse MTT(IR) in all 40 angiograms. Mean (SD) MTT(IR) was 5.0 (1.5) seconds in eyes with POAG and 4.7 (1.4) seconds in eyes with NTG. The difference was not statistically significant. There was a weak but significant correlation between the MD and MTT(IR) (MTT(IR) = 4.12-0.08*MD; r = -0.49, p = 0.0013). CONCLUSIONS: The results demonstrate that loss of neuronal tissue in glaucoma is combined with an effect on the retinal circulation and that the effect is similar in eyes with NTG and eyes with POAG.