Whole-mitochondrial genome sequencing in primary open-angle glaucoma using massively parallel sequencing identifies novel and known pathogenic variants.

PURPOSE: The aim of this study was to determine whether mutations in mitochondrial DNA play a role in high-pressure primary open-angle glaucoma (OMIM 137760) by analyzing new data from massively parallel sequencing of mitochondrial DNA. METHODS: Glaucoma patients with high-tension primary open-angle glaucoma and ethnically matched and age-matched control subjects without glaucoma were recruited. The entire human mitochondrial genome was amplified in two overlapping fragments by long-range polymerase chain reaction and used as a template for massively parallel sequencing on an Ion Torrent Personal Genome Machine. All variants were confirmed by conventional Sanger sequencing. RESULTS: Whole-mitochondrial genome sequencing was performed in 32 patients with primary open-angle glaucoma from India (n = 16) and Ireland (n = 16). In 16 of the 32 patients with primary open-angle glaucoma (50% of cases), there were 22 mitochondrial DNA mutations consisting of 7 novel mutations and 8 previously reported disease-associated sequence variants. Eight of 22 (36.4%) of the mitochondrial DNA mutations were in complex I mitochondrial genes. CONCLUSION: Massively parallel sequencing using the Ion Torrent Personal Genome Machine with confirmation by Sanger sequencing detected a pathogenic mitochondrial DNA mutation in 50% of the primary open-angle glaucoma cohort. Our findings support the emerging concept that mitochondrial dysfunction results in the development of glaucoma and, more specifically, that complex I defects play a significant role in primary open-angle glaucoma pathogenesis.

Prevalence of Anxiety and Depression in Patients With Primary Glaucoma in Western India.

PRCIS: Glaucoma can cause disturbance in psychological and emotional functioning of patients, leading to anxiety and depression, even early in the disease. Identification and management of these problems should be included as a part of the holistic approach for patient care. PURPOSE: The purpose of this study was to assess the prevalence of anxiety and depression in patients with primary glaucoma using a standard validated questionnaire. METHODOLOGY: A cross-sectional prevalence study was carried out on 200 patients attending the glaucoma outpatient clinic at a tertiary care eye hospital in Pune, India. After obtaining written consent, all patients underwent a thorough ophthalmic examination. Those with primary glaucoma were included in the study and classified on the basis of the Hodapp-Parrish-Anderson criteria. Participants were asked to respond to the Hospital Anxiety and Depression Scale (HADS) questionnaire, and responses were analyzed statistically. RESULTS: The mean HADS-Anxiety score was 4.5 (SD=3.4), while HADS-Depression was 4.1 (SD=3.8). The severity of the disease was associated with significantly higher HADS scores. Mean HADS-Anxiety scores were 3.1 (SD=2.9) for mild glaucoma, 4.4 (SD=2.6) for moderate, and 7.7 (SD=3.0) for advanced disease (P<0.001). Similarly, mean HADS-Depression scores were 2.0 (SD=2.6), 4.2 (SD=3.0), and 8.3 (SD=3.3), respectively for mild, moderate, and severe glaucoma (P<0.001). Based on HADS scores, a third of patients (34.5%) were symptomatic for anxiety or depression, out of which 25 (12.5%) could be classified as definite cases. Duration of treatment had no association with HADS scores. CONCLUSIONS: An association exists between the amount of visual loss among patients with glaucoma and symptoms of anxiety and depression, irrespective of disease duration. This information may help to choose treatment approaches most likely to be beneficial to the patients.

Comparison of bleb morphology by anterior segment optical coherence tomography and clinical outcome after phacotrabeculectomy with mitomycin C or Ologen implant.

PURPOSE: To compare the bleb morphology by Anterior Segment Optical Coherence Tomography (ASOCT) and clinical outcome after Phacotrabeculectomy with either mitomycin C or Ologen implant. METHODS: In a prospective interventional active controlled study, 93 patients aged 18 years and above underwent phacotrabeculectomy with either mitomycin C (53 eyes) or ologen implant (40 eyes), followed up for 12 months. The primary outcome measure was to note the evolution of bleb morphology by ASOCT in the two groups over 12 months. Secondary outcome measures were mean IOP, reduction in the need for anti-glaucoma medications, and complications seen in the two groups. RESULTS: All parameters in the two groups were comparable preoperatively (P>0.05). Best corrected visual acuity at 12 months was 0.38±0.27 in mitomycin group and 0.31±0.23 in ologen group (P=0.151). Post-operative IOP at 12 months was 14.09±3.1mmHg (95%CI 13.22-14.97) in mitomycin group, and 13.25±2.5 mmHg (95%CI 12.40-14.30) in ologen group (P=0.254). The mean number of medications was 0.36±0.68 in mitomycin group and 0.38+/-0.70 in ologen group at 12 months (P=0.91). Overall success was achieved in 98.1 % of patients in mitomycin group and 90 % of patients in ologen group at 12 months. No major sight-threatening complications were noted in any group. AS-OCT imaging at 12 months showed multiform reflectivity with multiple large cystic spaces in both groups, with good IOP control. CONCLUSION: Phacotrabeculectomy using Mitomycin C and Ologen implant resulted in similar morphologic and functioning blebs at one year with comparable efficacy in controlling intraocular pressure.

Assessment of psychosocial impact of primary glaucoma and its effect on quality of life of patients in Western India.

PURPOSE: : To assess the impact of primary glaucoma of varying severity and duration on psychosocial functioning and quality of life of patients. METHODS: A cross-sectional observational study was carried on 200 patients attending the glaucoma clinic of a tertiary care hospital in western India. After obtaining approval from the institutional ethics committee, written informed consent was taken. All patients underwent a thorough ophthalmic examination. Those with primary glaucoma were classified as per Hodapp-Parrish-Anderson criteria and asked to respond to the National Eye Institute Visual Function Questionnaire (NEIVFQ)-25 questionnaire. Responses were analyzed statistically. RESULTS: : Overall mean NEIVFQ 25 composite score was 74.4 ± 18.6. Mean scores were 87.0 (SD 7.2) for mild, 75.9 (SD 8.1) for moderate, and 47.0 (SD 13.7) for severe glaucoma groups. Lower scores were associated with males. Driving (62.2, SD 34.6) and ocular pain (63.5, SD 18.7) were maximally affected while color vision (90.1, SD 18.7) and social health (86.7, SD 20.1) were least affected. The duration of treatment had no effect on mean composite scores with impaired scores seen even in newly diagnosed cases. Age of the patient negatively correlated with NEIVFQ 25 composite score. CONCLUSION: : With disease progression, the psychosocial functioning of the patients is negatively affected. This effect is irrespective of treatment duration and newly diagnosed cases can have impaired Quality of life scores. Quantification of psychosocial status along with education and counseling for all patients may play a definitive role in customizing treatment and providing patients with a better quality of Life.

Comparative Clinical Study of Medically Controlled Nonsevere Chronic Primary Angle-closure Glaucoma with Coexisting Cataract Surgically Managed by Phacoemulsification as against Combined Phacotrabeculectomy.

PURPOSE: Comparative clinical study of medically controlled non-severe chronic Primary Angle Closure Glaucoma (PACG) with co-existing cataract surgically managed by phacoemulsification as against combined phacotrabeculectomy. METHODS: This randomized clinical trial was conducted between December 2011 and December 2013. Patients were randomly assigned to Phacoemulsification (PE) and Phacotrabeculectomy (PT) groups for surgery. Intraocular pressure, anti-glaucoma medications, Best Corrected Visual Acuity, anterior chamber angle widening and post-operative complications in both groups were compared after 12 months. RESULTS: There were 46 eyes with PACG in PE group and 45 in PT group. The IOP at 12 months in PE group was 11.5±1.3mmHg and 11.8±1.2mmHg in PT gr. (p = 0.28). The eyes requiring single anti-glaucoma medications at 12months in PE group was 0, PT group was 1 (p = 0. 495). The post op BCVA at 12months in PE group 0.3+-0.12 and 0.33±0.15 in PT group (p = 0.22). 3 cases in PT group required additional intervention whereas no additional intervention was required in PE group and this difference was statistically significant (p = 0.116). CONCLUSION: Phacoemulsification is equally effective in terms of intraocular pressure control and visual outcome as phacotrabeculectomy with better safety and less post-operative complication.

Effect of benzalkonium chloride-free latanoprost ophthalmic solution on ocular surface in patients with glaucoma.

INTRODUCTION: Benzalkonium chloride (BAK), included as a preservative in many topical treatments for glaucoma, induces significant toxicity and alters tear breakup time (TBUT). BAK-containing latanoprost, an ester prodrug of prostaglandin F2α, can cause ocular adverse events (AEs) associated with BAK. The purpose of this study was to evaluate the efficacy and safety of BAK-free latanoprost. PATIENTS AND METHODS: A prospective, open-label, single-arm, multicenter, 8-week study in patients with primary open-angle glaucoma or ocular hypertension taking BAK-containing latanoprost for ≥12 months was performed. Patients were switched to BAK-free latanoprost ophthalmic solution 0.005% administered once daily, and eyes were assessed after 28 and 56 days. Primary efficacy and safety variables were TBUT and treatment-emergent AEs, respectively. RESULTS: At day 56, 40 eyes were evaluable. Mean TBUT increased significantly from baseline (3.67±1.60 seconds) to 5.03±2.64 and 6.06±3.39 seconds after 28 and 56 days of treatment with BAK-free latanoprost (P<0.0001). Ocular Surface Disease Index(©) (OSDI(©)) score also decreased significantly to 12.06±13.40 and 7.06±10.75 at 28 and 56 days, respectively, versus baseline (18.09±18.61, P<0.0001). In addition, inferior corneal staining score decreased significantly to 0.53 from baseline (0.85, P=0.0033). A reduction in conjunctival hyperemia and intraocular pressure was observed at both time points. No treatment-related serious AEs were evident and 12 (26.08%) treatment-emergent AEs occurred in seven patients, with eye pain and irritation being the most frequent. No clinically significant changes in vital signs or slit lamp examinations were observed. CONCLUSION: Results indicate that switching from BAK-containing latanoprost to BAK-free latanoprost resulted in significant improvements in TBUT, OSDI(©) score, and inferior corneal staining score, and measurable reductions in conjunctival hyperemia score. Furthermore, BAK-free latanoprost was well tolerated with only mild-to-moderate and self-limiting AEs. BAK-free latanoprost appears to be effective in protecting ocular surface integrity in glaucoma patients but further studies are needed to confirm this beneficial effect.

An ultrasound biomicroscopic study of the anterior segment in Indian eyes with primary angle-closure glaucoma.

PURPOSE: To evaluate the presence of plateau iris in eyes with primary angle-closure glaucoma (PACG) after laser peripheral iridotomy by gonioscopy and ultrasound biomicroscopy and to evaluate the pathogenesis of this condition by comparing the UBM parameters of these eyes with those in normal subjects. PATIENTS AND METHODS: This prospective study was carried out in the Glaucoma clinic of a tertiary eye care center. A detailed clinical examination including applanation tonometry, indentation gonioscopy with a Sussman four-mirror gonioscope, and ultrasound biomicroscopic examination in one randomly selected eye of 55 patients (55 eyes) with PACG who had undergone laser peripheral iridotomy and 22 normal subjects (22 eyes). RESULTS: Among the PACG eyes, 40% (22/55) had an open angle (angle opening distance > 130 microns) and 60% (33/55) eyes had a narrow angle (angle opening distance

Is glaucoma blindness a disease of deprivation and ignorance? A case-control study for late presentation of glaucoma in India.

AIM: The aim was to identify the presenting symptoms and social risk factors for late presentation of primary glaucoma in newly diagnosed cases. MATERIALS AND METHODS: It was a case-control study in a tertiary eye care center in Maharashtra, India. Newly diagnosed patients with primary glaucoma were classified as cases (late presenters) where there was no perception of light in one eye or severe visual field loss affecting an area within 20° of fixation or a cup-disc (C:D) ratio ≥0.8 and controls (early presenters), presenting relative scotoma within 20° of fixation or a C:D ratio <0.8, but >0.5. All patients underwent a comprehensive ocular examination including gonioscopy, perimetry, and detailed family and social history. Occupation, education, and socioeconomic status were graded. SPSS version 12.0 was used, and univariate and multivariate logistic regression analysis was performed. RESULTS: Gradual progressive painless loss of vision was the commonest symptom (175, 87.5%). Primary angle closure glaucoma was more common in females (P = 0.001) and lower socioeconomic groups (P = 0.05). Patients who were less educated were more likely to have late presentation of glaucoma (P < 0.001, odds ratio = 0.07; 95% CI, 0.02-0.25). Knowledge of family history of glaucoma (P = 0.80, odds ratio = 1.16; 95% CI, 0.36-3.71) and eye clinic attendance in past 2 years still resulted in late presentation (P = 0.45, odds ratio = 1.34, 95% CI, 0.63-2.82). CONCLUSION: Lack of education and awareness of glaucoma were major risk factors for late presentation.