C677T variant in the methylentetrahydrofolate reductase gene is a genetic risk factor for primary open-angle glaucoma

PURPOSE: To estimate the prevalence of C677T single nucleotide polymorphism in the 5,10-methylentetrahydrofolate reductase (MTHFR) gene in primary open-angle glaucoma (POAG) and pseudoexfoliation open-angle glaucoma (PEXG). DESIGN: Case-control study METHODS: MTHFR was assessed in 147 patients (76 POAG, 71 PEXG) and 71 control subjects with cataract. Associations of genotypes were assessed by Armitage's trend test and the corresponding odds ratio (OR) for allele positivity with 95% confidence interval (CI). RESULTS: We observed significant evidence of a higher prevalence of C677T in POAG (9% homozygote, 49% heterozygote, 42% wildtype, P = .01, OR = 2.38, 95% CI 1.23-4.62), but not in PEXG (9% homozygote, 41% heterozygote, 50% wildtype, P = .09, OR = 1.78, 95% CI 0.91-3.50) compared with the controls (3% homozygote, 34% heterozygote, 63% wildtype). CONCLUSIONS: The MTHFR C677T variant leading to moderate hyperhomocysteinemia may play a role in the pathogenesis of POAG acting as a genetic risk factor.     

Combined phacoemulsification and goniotrephination in primary open-angle glaucoma and pseudoexfoliation glaucoma - a retrospective analysis

BACKGROUND: During the last few years combined cataract and glaucoma surgery is an established method to control intraocular pressure (IOP) and visual rehabilitation in patients with cataract and glaucoma. Despite this, there are currently only few data concerning the results of combined surgery for primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG). PATIENTS AND METHODS: To study the course of PEXG and POAG with respect to IOP regulation and visual acuity, 100 eyes with POAG (72 patients) and 22 with PEXG (19 patients) were evaluated which underwent a combined phacoemulsification and goniotrephination between 1993 and 1997. All patients had no glaucoma or other ocular surgery before. The mean follow up after operation was 39.5 (range 16 - 72) months. RESULTS: The mean preoperative IOP in PEXG (31.8 +/- 10.3 mm Hg) was significantly higher than in the POAG group (25.3 +/- 6.4 mm Hg) (p=0.0004). At follow up IOP decreased to 16.7 +/- 2.8 mm Hg (POAG) and 15.1 +/- 4.0 mm Hg (PEXG) (p < 0.0001). The absolute IOP lowering effect was significantly better for PEXG than for POAG (p=0.0003). All patients received medical treatment before surgery, whereas at follow up 59.0 % (POAG) and 81.8 % (PEXG) were untreated. The median preoperative visual acuity for the POAG was 0.32 (PEXG 0.25), visual outcome 0,63 (PEXG 0.5). CONCLUSION: The combined cataract and glaucoma surgery is a successful method of IOP control and visual rehabilitation. It seems that there is a tendency for a better efficiency and an untreated IOP regulation after surgery for PEXG. Thereby early surgical intervention could be an advantage for this glaucoma entity.     

Primary open-angle glaucoma presentation at a tertiary unit in Africa: intraocular pressure levels and visual status

AIM: To investigate the presentation of POAG at a tertiary referral hospital in East Africa, including intraocular pressures, visual status and management decisions. METHODS: Retrospective review of first-time presenters with POAG over a 6-month period. RESULTS: Of the 298 patients identified, mean age 57 years (n = 296, range = 14-88, SD = 14), 213 (72%) male, 122 (41%) had normal vision (using WHO better eye acuity criteria: visual impairment < 6/18, blind < 3/60) at presentation, 87 (30%) had visual impairment and 86 (29%) were blind. The mean presenting IOP was 32 mmHg (SD = 11) and 70% of the patients had a cup:disc ratio of 0.8 or worse in the better eye. Longer disease duration (OR = 1.20, 95% CI 1.04-1.39) and higher mean IOP (OR = 1.06, 95% CI 1.02-1.10) were associated with visual impairment or blindness. Intraocular pressure showed a negative linear correlation with presenting logMAR acuity (R(2) = 0.115, SE = 1.30, p < 0.0005). The mean IOP in eyes that had undergone trabeculectomy (19 mmHg, SD = 8, n = 17) was significantly (p < 0.0005) lower than that in eyes that had not (34 mmHg, SD = 12, n = 274). The referral rate for trabeculectomy was 158/275 (57%). Male sex (OR = 2.17, 95% CI 1.0-4.72), higher mean IOP (OR = 1.09, 95% CI 1.05-1.14) and not being blind (OR = 26.47, 95% CI 9.90-70.78) were associated with surgical referral. Of the 158 patients, 76 (48%) accepted surgery. CONCLUSIONS: A high proportion of patients presenting to our unit with POAG are visually impaired or blind and the higher their presenting IOP the poorer their visual acuity. Previous trabeculectomy was associated with lower IOPs and protection from visual impairment and blindness. Further training of clinic staff towards early surgical referral and investigation of gender barriers is required.     

Long-term results of viscocanalostomy in pseudoexfoliative and primary open angle glaucoma

Purpose: To document the outcome of viscocanalostomy (VC) alone or combined with phacoemulsification (phaco‐VC) in eyes with pseudoexfoliation glaucoma (PEXG) and primary open angle glaucoma (POAG). Methods: A prospective, comparative study of 314 eyes undergoing VC in two centres over 6 years was conducted. Main outcome measures were: (i) intraocular pressure (IOP) control (complete success was IOP ≤ 18 mmHg without medication and failure IOP > 18 mmHg); and (ii) requirement for Nd:YAG laser goniopuncture (YAG‐GP) if IOP > 21 mmHg. Results: In the POAG group, 174 eyes underwent phaco‐VC and 104 VC. In the PEX group, 20 eyes underwent phaco‐VC and 16 VC. At final follow up, complete success rate (CSR) was 76% for POAG phaco‐VC, 67% for POAG VC, 95% for PEXG phaco‐VC and 63% for PEXG VC with mean IOP reduction of 29.9%, 40%, 42.5% and 51%, respectively. Without YAG‐GP, by 3 years postoperatively the failure rate was 100% for PEXG eyes and 21% for POAG eyes undergoing VC alone, but PEXG eyes undergoing phaco‐VC were 100% successful. CSR for YAG‐GP was 92% in PEXG VC eyes and 55% in POAG VC eyes. Conclusions: In phakic eyes with PEXG undergoing VC, an absolute requirement for long‐term success was YAG‐GP. This was not the case in POAG eyes or PEXG eyes undergoing phaco‐VC. Late IOP rise in phakic PEXG eyes and restoration of IOP control following YAG‐GP suggests that continued release of PEX material from the lens capsule with time blocks the outflow through the trabecular‐Descemetic window created by VC.     

Influence of Family History as a Risk Factor on Primary Angle Closure and Primary Open Angle Glaucoma in a Chinese population

Purpose: To identify the likelihood of family history as a risk factor for the presence and severity of primary angle closure (PAC) and primary open angle glaucoma (POAG) in a Chinese population.

Methods: All participants were asked to complete a questionnaire and undergo a comprehensive eye examination. Past history of hypertension, diabetes mellitus, hyperopia, high myopia, and family history of glaucoma were recorded. For those patients with a family history of glaucoma, the relationship between the patient and the affected relatives has been specified.

Results: A total of 332 PAC patients, 228 POAG patients and 193 controls were included. Of the 332 PAC patients, 83 (25.00%) had glaucoma family history. Characteristic-adjusted odds ratio (OR) of family history for PAC was 4.82 [95% confidence interval (CI): 2.08–11.19] and for severity of PAC was 1.61 (95% CI: 1.05–2.49). Among first-relatives only parents account for the family history rate of PAC [OR 8.76 (95% CI: 2.00–38.32)]. Of the 228 POAG patients, 49 (21.49%) had a family history of glaucoma. Odds ratio for POAG was 8.38 (95% CI: 3.33–21.07) and for severity of POAG was 1.81 (95% CI: 1.05–3.14). Unlike patients with PAC, only siblings and offspring account for the family history rate of POAG [OR 8.99 (95% CI: 2.38–33.99) and OR 19.23 (95% CI: 1.53–241.24) respectively].

Conclusion: Our study showed that a family history of glaucoma is associated with the presence and severity of PAC and POAG. This supports the finding that screening first-degree relatives will be an effective way to detect glaucoma in a population.     

Association of ABO blood groups with glaucoma in the Pakistani population

Objective: To study the association of blood groups with different types of glaucoma including primary open-angle glaucoma (POAG), primary closed-angle glaucoma (PCAG), and pseudoexfoliative glaucoma (PEXG) in the Pakistani population.Study Design: The present study was a prospective case control study.Participants: ABO and Rh blood groups were analyzed in 2046 controls and 477 glaucoma patients (220 POAG, 146 PCAG, and 111 PEXG).Methods: Hemagglutination patterns were used to determine the prevalence of the ABO and Rh blood groups in all the subjects. Logistic regression analysis was carried out to evaluate any association of the different blood groups with glaucoma.Results: In the present study, the percentage of blood groups A, B, AB, and O in patients was found to be 19%, 41%, 10%, and 30%, and in the control group, the values were 26%, 31%, 12%, and 31%, respectively. A significant positive association was found between the B blood group and glaucoma (p value < 0.05, odds ratio [OR] 1.5, and χ² 15.8). Logistic regression analysis revealed that the blood group B was associated with all types of glaucoma with OR of 1.35 (95% CI 1.01-1.80; p = 0.04) for POAG, 1.71 (95% CI 1.21-2.40; p = 0.002) for PCAG, and 1.61 (95% CI 1.09-2.36; p = 0.016) for PEXG. POAG was also found to be associated with the Rh- allele (p < 0.05) with an OR of 4.05 (95% CI 2.98-5.51), as compared with controls.Conclusions: In the Pakistani patient cohort, blood group B is associated with all types of glaucoma and the Rh-allele is associated only with POAG.     

The Effect of MTHFR Ala222Val Polymorphism on Open-angle Glaucoma: A Meta-analysis

Glaucoma is the second leading cause of irreversible blindness worldwide, among which primary open-angle glaucoma (POAG) is the most common form of glaucoma in some populations. To date, published data on the association between MTHFR (Ala222Val) polymorphism and POAG risk are still inconclusive. In this work, we performed a meta-analysis of available case-control study in order to assess the association between MTHFR (Ala222Val) polymorphism and POAG susceptibility. In total we compiled 13 studies (1970 POAG patients and 1712 control subjects) into the meta-analysis. Overall, no obvious associations between MTHFR (Ala222Val) polymorphism and POAG susceptibility was found under all four genetic models (Val/Val versus Ala/Ala: OR?=?1.05, 95% CI?=?0.77–1.43; Ala/Val versus Ala/Ala: OR?=?1.05, 95% CI?=?0.86–1.26; Ala/Val + Val/Val versus Ala/Ala: OR?=?1.08, 95% CI?=?0.87–1.34; Val/Val versus Ala/Val + Ala/Ala: OR?=?1.14, 95% CI?=?0.67–1.92). In the stratified analysis by ethnicity, significant associations were still not observed in all genetic models. In conclusion, based on 13 eligible studies, the result provided strong evidences that MTHFR Ala222Val polymorphism is not associated with POAG.     

Five-year risk of progression of ocular hypertension to primary open angle glaucoma. A population-based study

PURPOSE: To report the progression of ocular hypertension (OHT) to primary open angle glaucoma (POAG) during a 5-year follow up of a population-based sample. METHODS: Twenty-nine patients diagnosed to have OHT and 110 randomly selected normals from a population-based study in 1995 were invited for ocular examination in 2000. All patients underwent a complete ophthalmic examination; including the daytime diurnal variation of intraocular pressure (IOP) and measurement of central corneal thickness (CCT). The "corrected" IOP was used for analysis. Progression to POAG was based on typical optic disc changes with corresponding field defects on automated perimetry. RESULTS: Twenty-five of the 29 persons with OHT who could be contacted were examined. After correcting for CCT, two persons were reclassified as normal. Four of 23 (17.4%; 95% CI: 1.95-32.75) had progressed to POAG. One person amongst the 110 normals progressed to normal tension glaucoma (NTG). The relative risk of progression amongst OHT was 19.1 (95% CI: 2.2-163.4). All those who progressed had bilateral OHT. The mean and peak IOP in those who progressed was 25.4 mm Hg and 29.3 mm Hg compared to 23.9 mm Hg and 25.7 mm Hg in those who did not. Those who progressed had more than 8 mm Hg diurnal variation. The diurnal variation was less than 6 mm Hg in those who did not progress. No patient developed blindness due to glaucoma. CONCLUSION: The 5-year incidence of POAG amongst OHT in this population was 17.4% (3.5% per year). Bilateral OHT, higher peak IOP and large diurnal variation may be the risk factors for progression.     

Management of the open angle glaucoma in patients with central/hemicentral retinal vein occlusions

AIM: To prospectively assess the cumulative prevalence and management of open angle glaucoma (OAG), including primary open angle glaucoma (POAG) with high and normal-pressure, as well as pseudoexfoliative glaucoma (PEXG), in patients with central/hemicentral retinal vein occlusions (RVOs) over a 3-year follow-up period. METHODS: The study encompassed 57 patients with unilateral acute central/hemicentral RVOs. A complete ophthalmic examination of both eyes was undertaken for all patients. Patients with OAGs associated with central/hemicentral RVOs were treated with the current ocular hypotensive medications used worldwide and/or surgery and aimed to reduce the intraocular pressure (IOP) by 30% from baseline values for the 3 OAG forms existing in our series. The cumulative prevalence of OAG and the efficacy of treatment were evaluated. RESULTS: OAG was observed in 3 clinical forms, namely, POAG with increased IOP in 4 patients, POAG with normal IOP in 3 patients, and PEXG in 3 patients. The cumulative prevalence of OAG was 19.6% (95%CI: 8.7-30.5). Using available ocular hypotensive medications (8 patients) and trabeculectomy (2 patients), the IOP decreased significantly from 24.3±4.36 mm Hg to 16.55±2.85 mm Hg, a reduction of 31.89% compared with baseline values. Glaucoma progression was not detected in any of the cases. CONCLUSION: The high value of the cumulative prevalence of OAG is a risk factor for the development of venous occlusion. The treatment of glaucoma prevented its progression over a follow-up period of 3y.     

Factors associated with undiagnosed open-angle glaucoma: the Thessaloniki Eye Study

PURPOSE: To identify factors associated with undiagnosed open-angle glaucoma (OAG), primary open-angle glaucoma (POAG), and pseudoexfoliative glaucoma (PEXG) in an elderly population in Thessaloniki, Greece. DESIGN: Cross-sectional population-based study. METHODS: Randomly selected subjects > or =60 years (n = 2,554) participated in the study. Subjects were classified as having POAG or PEXG according to specific criteria and using a two-scale definition of glaucoma. Undiagnosed glaucoma was defined as absence of either prior diagnosis of glaucoma or ocular hypertension or prior medical treatment for glaucoma or prior glaucoma surgery. Logistic regression analyses were performed with age, gender, family history of glaucoma, history of cataract surgery, visual acuity, vertical cup-to-disk (C/D) ratio, intraocular pressure, Advanced Glaucoma Intervention Study visual field score, time since last eye doctor visit, and type of OAG as covariates. RESULTS: The prevalence of undiagnosed glaucoma was 57.1% (56/98) for POAG, significantly higher than the prevalence of 34.9% (15/43) for PEXG (P = .017). POAG patients presented three to four times increased risk to be undiagnosed compared with PEXG patients (P = .02 and P = .04, respectively). Patients with OAG who had not visited an ophthalmologist during the last year had six times an increased risk to be undiagnosed (P = .003). In POAG, smaller vertical C/D ratio was statistically significantly associated with an increased risk to be undiagnosed (P = .008). CONCLUSIONS: Lack of regular visits to an ophthalmologist was a major factor for undiagnosed OAG. POAG was more likely to be undiagnosed than PEXG. Since C/D ratio was associated with undiagnosed POAG, standardized protocols involving thorough evaluation of the optic disk are recommended for ophthalmologists.     

Phacoviscocanalostomy in pseudoexfoliation glaucoma versus primary open-angle glaucoma

Objective: To compare the outcome of phacoviscocanalostomy in Pseudoexfoliation glaucoma (PEXG) versus that in primary open-angle glaucoma (POAG).Design: Prospective comparative study.Participants: Sixty eyes of 60 patients who underwent phacoviscocanalostomy for cataract and medically uncontrolled PEXG (30 eyes) or POAG (30 eyes).Methods: Success rate was based on intraocular pressure (IOP) reduction and need for antiglaucoma medication. Visual acuity (VA) and complication rates were secondary outcomes.Results: The mean follow-up was 19.7 months (range, 12–36 months). The mean IOP values in both groups were significantly less than the preoperative values at all postoperative intervals (p < 0.001). From 1 month onward, the decrease in IOP was more dramatic in PEXG eyes than in POAG eyes (p < 0.05). At last visit, the mean percentage of IOP reduction was 49.7% in the PEXG group and 30.9% in the POAG group. All study eyes required decreased antiglaucoma medications and showed improved VA postoperatively. Transient complications included Descemet's membrane microperforations, macroperforation, zonular dehiscence, and postoperative IOP spike. No eyes developed trabeculectomy-type bleb, hyphema, fibrin exudation, or bleb-related complications.Conclusions: Phacoviscocanalostomy achieved excellent IOP control and VA improvement in both PEXG and POAG groups. PEXG demonstrated greater IOP reduction and fewer postoperative medications than POAG. The complication rate was low and did not affect surgical outcome. Phacoviscocanalostomy can be an effective and safe surgical alternative to phacotrabeculectomy in both groups of patients.     

Rates of visual field progression in clinical glaucoma care

Purpose: To investigate rates of visual field progression and factors associated with progression rate in open‐angle glaucoma in clinical glaucoma care. Methods: We performed a retrospective chart review of all patients with manifest primary open‐angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) followed ≥ 5 years with ≥5 SITA Standard fields. Exclusion criteria were minimal. Demographics, intraocular pressure values (IOP), treatment and treatment changes, and visual field (VF) data were recorded. VF progression rates were calculated as slopes of mean deviation (MD) over time. Results: Five hundred and eighty‐three patients were eligible. Three hundred and sixty‐seven (62%) had POAG and 221 (38%) PEXG. Median MD at study start was ?10.0 dB. Mean follow‐up time was 7.8 years (SD ± 1.2); mean number of VF tests was 8.9 (SD ± 2.8). Progression rates varied very much among patients with a mean of ?0.80 dB/year (SD ± 0.82; median rate, ?0.62), and 5.6% of patients progressed at rates worse than ?2.5 dB per year A negative slope of MD values was observed in 89% of patients. Mean IOP of all visits decreased over the study period from 20.15 to 18.10 mmHg. Higher age and mean IOP, and more intensive treatment were associated with more rapid progression, while PEXG and IOP variation were not, if treatment intensity was taken into account. Conclusion: Rates of visual field progression in manifest glaucoma with field loss in ordinary clinical care were highly variable. Progression rates rapid enough to influence quality of life were common.     

Glaucoma in a rural population of southern India: the Aravind comprehensive eye survey

PURPOSE: To determine the prevalence of glaucoma and risk factors for primary open-angle glaucoma in a rural population of southern India. DESIGN: A population-based cross-sectional study. PARTICIPANTS: A total of 5150 subjects aged 40 years and older from 50 clusters representative of three southern districts of Tamil Nadu in southern India. METHODS: All participants had a comprehensive eye examination at the base hospital, including visual acuity using logarithm of the minimum angle of resolution illiterate E charts and refraction, slit-lamp biomicroscopy, gonioscopy, applanation tonometry, dilated fundus examinations, and automated central 24-2 full-threshold perimetry. MAIN OUTCOME MEASURES: Definite primary open-angle glaucoma (POAG) was defined as angles open on gonioscopy and glaucomatous optic disc changes with matching visual field defects, whereas ocular hypertension was defined as intraocular pressure (IOP) greater than 21 mmHg without glaucomatous optic disc damage and visual field defects in the presence of an open angle. Manifest primary angle-closure glaucoma (PACG) was defined as glaucomatous optic disc damage or glaucomatous visual field defects with the anterior chamber angle partly or totally closed, appositional angle closure or synechiae in the angle, and absence of signs of secondary angle closure. Secondary glaucoma was defined as glaucomatous optic nerve damage and/or visual field abnormalities suggestive of glaucoma with ocular disorders that contribute to a secondary elevation in IOP. RESULTS: The prevalence (95% confidence interval) of any glaucoma was 2.6% (2.2, 3.0), of POAG it was 1.7% (1.3, 2.1), and if PACG it was 0.5% (0.3, 0.7), and secondary glaucoma excluding pseudoexfoliation was 0.3% (0.2,0.5). On multivariate analysis, increasing age, male gender, myopia greater than 1 diopter, and pseudoexfoliation were significantly associated with POAG. After best correction, 18 persons (20.9%) with POAG were blind in either eye because of glaucoma, including 6 who were bilaterally blind and an additional 12 persons with unilateral blindness because of glaucomatous optic neuropathy in that eye. Of those identified with POAG, 93.0% had not been previously diagnosed with POAG. CONCLUSIONS: The prevalence of glaucoma in this population is not lower than that reported for white populations elsewhere. A large proportion of those with POAG had not been previously diagnosed. One fifth of those with POAG had blindness in one or both eyes from glaucoma. Early detection of glaucoma in this population will reduce the burden of blindness in India.     

Prevalence and risk factors for primary open-angle glaucoma in a rural northeast China population: a population-based survey in Bin County, Harbin

Purpose

To estimate the prevalence and associated risk factors of primary open-angle glaucoma (POAG) in a rural population in northeast China.

Methods

A population-based survey was conducted within Bin County, Harbin of northeast China. Glaucoma was diagnosed using International Society of Geographical and Epidemiological Ophthalmology criteria. All the subjects underwent a complete ophthalmic examination.

Results

A total of 4956 (86.0%) of 5762 subjects aged 40 years or older were examined. The mean intraocular pressure (IOP) of right eyes was 14.0 (95% confidence interval (CI), 13.9 to 14.1) mm Hg. The prevalence of POAG was 0.71% (35/4956, 95% CI, 0.47 to 0.93). In these POAG subjects, 17 (48.6%) had elevated IOP >21 mm Hg in either eye, 3 (8.8%) participants had been treated by laser trabeculoplasty or trabeculectomy and were known to have POAG. Vision impairment to varying degrees was present in 20 subjects (58.8%) with 1 subject blind in both eyes and 8 subjects blind in one eye. On multivariate analysis, age, family history of glaucoma, systemic hypertension, and IOP were regarded as significant independent risk factors.

Conclusions

POAG is a disease of serious consequence and of low diagnosis and treatment rates in rural northeast China. Age, family history of glaucoma, systemic hypertension, and IOP remain as significant independent risk factors for POAG.     

Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic

OBJECTIVE: To assess whether central corneal thickness (CCT) is a confounding factor in the classification of patients attending for glaucoma assessment in a district general hospital. DESIGN: Cross-sectional study by a single observer. PARTICIPANTS: Patients attending a general ophthalmic clinic: 235 clinically normal eyes, 52 eyes with normal-tension glaucoma (NTG), 335 eyes with primary open-angle glaucoma (POAG), 12 eyes with pseudoexfoliative glaucoma (PXE), 42 eyes with chronic angle closure glaucoma (CACG), and 232 glaucoma suspect (GS) eyes. INTERVENTION: Central corneal thickness was measured using ultrasonic pachymetry. MAIN OUTCOME MEASURE: Correlation of CCT and diagnosis. RESULTS: Mean CCT was 553.9 microm (95% confidence intervals [CI] for the mean, 549.0-558.8 microm) in the clinically normal eyes, 550.1 microm (95% CI, 546.6-553.7 microm) in the POAG eyes, 514.0 microm (95% CI, 504.8-523.3 microm) in the NTG eyes, 530.7 microm (95% CI, 511.2-550.1 microm) in the PXE eyes, 559.9 microm (95% CI, 546.8-573.0 microm) in the CACG eyes, and 579.5 microm (95% CI, 574.8-584.1 microm) in the GS eyes. The differences of mean CCT between the groups were highly significant (P< 0.001 analysis of variance). Eighty-five percent of eyes with NTG and only 36% of eyes with POAG had a mean CCT of 540 microm or less. Thirteen percent of eyes with POAG and 42% of GS eyes had a mean CCT greater than 585 microm. CONCLUSIONS: The CCT measurement is desirable in patients attending for glaucoma assessment in a district general hospital to avoid misclassification resulting from the relationship between CCT and tonometric pressure. Central corneal thickness alone is not an accurate predictor for the clinical diagnosis in this group of eyes. However, many eyes diagnosed as having NTG have thin corneas, which would tend to lower the tonometrically recorded intraocular pressure (IOP), so the finding of a less-than-normal thickness cornea introduces some doubt as to the diagnosis of NTG. For the GS eyes, most eyes had thick corneas, which would tend to increase the tonometrically recorded IOP. Thus, GS eyes with modest elevation of IOP and a thick cornea may be at low risk of progressing to POAG. Thus, many patients with "high IOPs" and a thick CCT do not necessarily have high IOPs and may not need to be followed as GS eyes.     

MicroRNA-related polymorphisms in pseudoexfoliation syndrome,pseudoexfoliative glaucoma,and primary open-angle glaucoma

Background: Pseudoexfoliation syndrome (PEX) and glaucoma (pseudoexfoliative glaucoma; PEXG, primary open-angle glaucoma; POAG) have mainly been studied for their associations with genes’ polymorphisms. The purpose of this exploratory study was to investigate the role of polymorphisms in genes encoding for micro RNAs (miRNAs) and in genes related to miRNA biogenesis.

Material and Methods: In the present genetic association study, ninety-two polymorphisms were investigated for their contribution to PEX (n = 203), PEXG (n = 38), and POAG (n = 40) pathogenesis compared to a control group (n = 188). The next generation sequencing (NGS) genotypic analysis revealed data for additional 28 variants.

Results: A protective association was found between PEX and polymorphism 11382316 (mir-3161) [odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.47–0.86, p = 0.003], rs2155248 (mir-1304) [OR = 0.66, 95%CI: 0.47–0.94, p = 0.019], and rs28635903 (mir-1268a) [OR = 0.30, 95%CI: 0.10–0.94, p = 0.029]. Polymorphism rs113297757 (mir-3196) was associated with an increased risk of POAG [OR = 7.75, 95%CI: 2.13–28.76, p = 3 × 10^?4]. Polymorphism rs1057035 (DICER) and rs55671916 (XPO5) in the 3?-UTR of genes related to miRNA biogenesis was associated with decreased risk of PEX [OR = 0.65, 95%CI: 0.46–0.92, p = 0.014] and increased risk of PEXG [OR = 2.84, 95%CI: 1.02–7.94, p = 0.038], respectively. The aforementioned associations according to the allelic model were further supported by the genotypic models of statistical analyses.

Conclusions: This is the first study to report distinct associations of PEX, PEXG, and POAG in the same population with variants of genes involved in miRNA biogenesis and with miRNA genes’ polymorphisms. Further studies in larger groups of patients of various origins are needed to confirm the reported preliminary results.     

Quantifying the effect of intraocular pressure reduction on the occurrence of glaucoma

Purpose: To estimate the effect of reducing intraocular pressure (IOP) on: (i) the incidence of primary open‐angle glaucoma (POAG) in patients with ocular hypertension (OH), and (ii) the progression of glaucoma. Methods: A meta‐analysis of relevant randomized controlled trials was conducted. A literature search was performed to identify trials with: a randomized comparison of IOP‐lowering intervention versus placebo or no treatment; visual field loss or optic disc changes as outcome; and follow‐up >6 months. A pooled relative risk (RR) was calculated by a random effects model. Risk reduction of glaucoma conversion per mmHg of IOP reduction was quantified in a meta‐regression model. Results: We identified nine OH and one POAG trials. A meta‐analysis of OH trials gives a pooled RR of 0.61 [95% confidence interval (CI) 0.45–0.83]. A meta‐regression shows a decrease of the RR of glaucoma conversion by 14% with each mmHg extra IOP reduction (P = 0.045). No meta‐analysis of POAG trials was performed because only one study has been identified. Conclusion: There is sufficient evidence that OH therapy reduces the risk of conversion to glaucoma. This risk reduction increases with greater IOP reduction.     

Blindness and glaucoma: a comparison of patients progressing to blindness from glaucoma with patients maintaining vision

PURPOSE: To compare patients becoming legally blind from glaucoma with those who did not go blind. DESIGN: Retrospective, cohort, and case-control study. METHODS: A retrospective community-based longitudinal study of residents of Olmsted County, Minnesota, who were newly diagnosed with open-angle glaucoma between 1965 and 1980 and followed through 1998. A case-control study was performed comparing patients progressing to legal blindness from glaucoma with aged-matched and visual field-matched patients not progressing to blindness. RESULTS: Fifty-six of 290 patients progressed to legal blindness in at least one eye over the 34-year period of the study. Most who progressed to blindness had moderate to advanced visual field loss at the time of diagnosis of glaucoma. Those becoming legally blind had mean intraocular pressures (IOP) on therapy lower than or similar to patients who did not go blind, although the variability of IOP was higher in the blind group. Different susceptibilities to IOP were apparent, as some eyes with initially normal disks and visual fields became blind at an IOP of 20 mm, while others did not worsen. Changes in medical therapy after progression of visual field damage were less effective in lowering IOP in the group becoming blind than in the nonblind group. CONCLUSIONS: Patients at greatest risk of blindness had visual field loss at the time of diagnosis of glaucoma. Different susceptibilities to IOP were apparent, with some patients becoming blind at pressures that others tolerated without significant progression. This suggests that continued monitoring of visual fields and reassessment of target IOP levels when field damage occurs are fundamental in the management of glaucoma.     

Nutritional,lifestyle and environmental factors in ocular hypertension and primary open‐angle glaucoma: an exploratory case–control study

Purpose: To evaluate known and potential risk factors, including nutritional, lifestyle and environmental factors, differentiating patients with high‐tension primary open‐angle glaucoma (POAG) from control subjects with ocular hypertension (OHT). Methods: In 2006–2007, 111 French ophthalmologists prospectively enrolled 339 cases of POAG and 339 age‐matched controls with OHT. After a clinical examination with assessment of ocular risk factors, the ophthalmologist filled, during face‐to‐face interview, a detailed questionnaire developed by nutritionists and epidemiologist on lifestyle and environmental risk factors, including socio‐demographic variables, dietary habits related to omega‐3 fatty acids intake, smoking and alcohol drinking and professional exposure to pesticides and other chemicals. Associations of POAG with risk factors were estimated using conditional logistic regression, with adjustment for age, gender and duration of disease. Results: In the final multivariate model, by comparison with OHT, POAG was significantly associated with more frequent use of pesticides during the professional life [OR = 2.65, 95% confidence interval (CI): 1.04–6.78, p = 0.04] and with low consumption of fatty fish (OR = 2.14, 95% CI: 1.10–4.17, p = 0.02) and walnuts (OR = 2.02, 95% CI: 1.18–3.47, p = 0.01). POAG was also associated with higher frequency of heavy smoking (40 pack‐years or more, OR = 3.93, 95% CI: 1.12–13.80, p = 0.03) but not with moderate (20–40 pack‐years) and light smoking (<20 pack‐years). Conclusions: These exploratory observations suggest a protective effect of omega‐3 fatty acids and a deleterious effect of heavy smoking and professional exposure to pesticides in POAG. This will need to be confirmed in future studies.     

Pathophysiologic changes in the optic nerves of eyes with primary open angle and pseudoexfoliation glaucoma

PURPOSE: To determine whether differences in the optic nerve occur in eyes with primary versus secondary open-angle glaucoma. METHODS: Optic nerves obtained at autopsy from 36 eyes with primary open-angle glaucoma (POAG) and 15 with pseudoexfoliation glaucoma (PEXG) were studied quantitatively and qualitatively. Axon counts, fibrosis, capillary number and density, and arteriosclerotic changes were assessed in the postlaminar optic nerve and compared to normal age-matched autopsy eyes. Changes in composition of extracellular matrix components were evaluated by immunohistochemistry and electron microscopy. RESULTS: Marked differences were found between POAG and PEXG. Axon loss in eyes with POAG but not in PEXG was associated with increasing connective tissue in the septa and surrounding the central retinal vessels, including increased amounts of type IV and VI collagen. The total number of capillaries decreased with the loss of axons in both POAG and PEXG. POAG nerves, however, had a decrease in the density of capillaries, whereas in PEXG the capillary density did not change with axon loss. Arteriosclerotic changes were more common in glaucomatous eyes than in age-matched control eyes. CONCLUSIONS: The difference in morphology of the optic nerves between POAG and PEXG indicates that in eyes with POAG, elevated IOP cannot be the only pathogenetic factor in glaucomatous optic neuropathy. Additional factors, inducing fibrosis and loss of capillaries, seem to be involved. Such additional factors may also contribute to the clinical finding in POAG that nerves can become damaged without elevation of intraocular pressure.