Untargeted metabolomics in the aqueous humor reveals the involvement of TAAR pathway in glaucoma.

Understanding the metabolic dysfunctions and underlying complex pathological mechanisms of neurodegeneration in glaucoma could help discover disease pathways, identify novel biomarkers, and rationalize newer therapeutics. Therefore, we aimed to investigate the local metabolomic alterations in the aqueous humor and plasma of primary glaucomatous patients. This study cohort comprised primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), and cataract control groups. Aqueous humor and plasma samples were collected from patients undergoing trabeculectomy or cataract surgery and subjected to high-resolution mass spectrometry (HRMS) analysis. Spectral information was processed, and the acquired data were subjected to uni-variate as well as multi-variate statistical analyses using MetaboAnalyst ver5.0. To further understand the localized metabolic abnormalities in glaucoma, metabolites affected in aqueous humor were distinguished from metabolites altered in plasma in this study. Nine and twelve metabolites were found to be significantly altered (p < 0.05, variable importance of projection >1 and log2 fold change ≥0.58/≤ -0.58) in the aqueous humor of PACG and POAG patients, respectively. The galactose and amino acid metabolic pathways were locally affected in the PACG and POAG groups, respectively. Based on the observation of the previous findings, gene expression profiles of trace amine-associated receptor-1 (TAAR-1) were studied in rat ocular tissues. The pharmacodynamics of TAAR-1 were explored in rabbits using topical administration of its agonist, ß-phenyl-ethylamine (ß-PEA). TAAR-1 was expressed in the rat's iris-ciliary body, optic nerve, lens, and cornea. ß-PEA elicited a mydriatic response in rabbit eyes, without altering intraocular pressure. Targeted analysis of ß-PEA levels in the aqueous humor of POAG patients showed an insignificant elevation. This study provides new insights regarding alterations in both localized and systemic metabolites in primary glaucomatous patients. This study also demonstrated the propensity of ß-PEA to cause an adrenergic response through the TAAR-1 pathway.

Elevated histamine levels in aqueous humor of patients with glaucoma.

Purpose: Neurotransmitters (NTs) are the key mediators of essential ocular functions, such as processing the visual functions of the retina, maintaining homeostasis of aqueous humor, and regulating ocular blood flow. This study aims to determine variations in the levels of L-glutamate and γ-aminobutyric acid (GABA), histaminergic, adrenergic, cholinergic, and serotonergic NTs in patients with primary glaucoma versus patients with cataract. Methods: This case-control study involved three age-matched groups of patients with primary open angle glaucoma (POAG, n = 14), primary angle closure glaucoma (PACG, n = 21), and cataract (control, n = 19). Patients' aqueous humor and plasma were collected, snap frozen at -80 °C, and subjected to ultrasensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis for quantification of NTs. Results: Baseline intraocular pressure and the cup-to-disc ratio were found to be statistically significantly elevated in the POAG and PACG groups compared to the cataract control group. In aqueous humor, histamine was found to be statistically significantly elevated (5-fold, p<0.0001), whereas 1-methyl histamine was statistically significantly decreased (p<0.05) in POAG compared to the control group. A statistically significant increase in L-glutamate and GABA was observed among both patient groups with glaucoma compared to the cataract control group. Adrenaline was found to be elevated only in the PACG group (2.7-fold, p<0.05). No statistically significant difference was observed among the plasma NT levels between the groups. Conclusions: This study demonstrated the prominent role of the histaminergic system apart from autonomic mechanisms in the progression of glaucoma. Elevated L-glutamate and GABA could be due to retinal ganglionic cell death. Further studies are required to evaluate the effects of histamine on Müller cell dysfunction.

The role of clinical examination of the optic nerve head in glaucoma today.

PURPOSE OF REVIEW: The study was undertaken to assess the current importance of clinical examination of the optic nerve head (ONH) in glaucoma management. RECENT FINDINGS: ONH changes in glaucoma are easily assessed with good specificity on examination, whereas imaging has not been able to identify pallor of the neuroretinal rim (NRR), disc hemorrhages, or vascular signs of acquired cupping. Glaucomatous neuropathy in primary open angle glaucoma (POAG) has extensive databases on imaging machines, however, other glaucomas such as primary angle closure glaucoma (PACG), juvenile open angle glaucoma (JOAG), congenital, and secondary glaucomas have been reported to have a significantly different ONH morphology. Clinical evaluation with knowledge of the underlying cause of glaucoma allows easy diagnosis of any abnormality, whereas the absence of an imaging database in such eyes makes diagnosis difficult on optical coherence tomography (OCT) and so forth. In eyes with congenital anomalies and dysplastic discs, clinical examination and history provide better identification of glaucomatous damage. Staging of glaucoma on ONH examination when perimetry is unreliable provides a means of determining the amount of damage and appropriate reduction of intraocular pressure (IOP). SUMMARY: Clinical examination of the ONH is very relevant for screening, diagnosis, staging, and management of all glaucomas, and is irreplaceable in detecting nonglaucomatous causes of ONH cupping and visual field defects similar to those in glaucoma.

Improving long-term intraocular pressure and visual outcomes in eyes with aniridic glaucoma.

PURPOSE: To study the long-term intraocular pressure (IOP) and visual outcomes in treated aniridic glaucoma. METHODS: A retrospective chart review of patients with aniridia and glaucoma, with ≥ 2-year follow-up, was performed. Eyes in early glaucomatous stages were medically managed, while moderate-severe stage eyes underwent a trabeculectomy with mitomycin-c (MMC). Success was termed 'complete' when average final IOP was ≤ 18 mmHg without usage of glaucoma medications, and 'qualified' when with/without topical glaucoma therapy. A significant change in vision was defined as > 2-line change on Snellen vision chart or > 0.2 change in logMAR units in in either direction (better or worse). RESULTS: Thirty-five eyes of 20 patients were included. The mean duration of follow-up was 7.29 ± 5.75 years. Associated ocular anomalies were present in 19 eyes (54.29%). Twelve eyes (34.28%) were maintained on medical management, while 23 eyes (65.71%) had undergone a trabeculectomy with MMC. The mean baseline IOP was 31.46 ± 6.34 mmHg, and mean IOP on last follow-up was 13.25 ± 5.82 mmHg, p < 0.001. Seventy-five percent of the medically managed eyes achieved an IOP ≤ 18 mmHg. 52.17% and 95.65% of the surgically treated eyes achieved 'complete' and 'qualified' success respectively. The median best corrected visual acuity (BCVA) at baseline was 1.48(0.6-2) logMAR units and on final follow-up was 1.3 (0.48-5) logMAR units, p = 0.21. Fifty percent of the eyes remained stable, 35.71% showed an improvement and 14.29% a deterioration of > 0.2 logMAR units. Patients with a longer follow-up (> 10 years) and those who had undergone a trabeculectomy with MMC were more likely to show good IOP control (p = 0.003; p = 0.004 respectively). CONCLUSION: Aniridic glaucoma can be managed efficiently by medications in early glaucomatous neuropathy, and with trabeculectomy augmented with mitomycin-C and releasable sutures for more advanced glaucomas, offering favourable long-term IOP control, visual stability and safety.

Effect of airway device and depth of anesthesia on intra-ocular pressure measurement during general anesthesia in children: A randomized controlled trial.

BACKGROUND AND AIMS: Accurate measurement of intraocular pressure (IOP) under anaesthesia is essential for diagnosis and further management of pediatric glaucoma patients. However, depth of anaesthesia and use of airway device like laryngeal mask airway (LMA) or endotracheal tube can influence IOP values measured. We planned this study to compare change of IOP with facemask or LMA. Change of IOP at varying depth of anaesthesia was also assessed. MATERIAL AND METHODS: After Institutional ethical clearance and informed parental consent, 89 children of glaucoma aged 0-12 years were included in this prospective randomized controlled trial. The children were randomized to facemask (Group M) and LMA (Group L). Sevoflurane was the sole general anaesthetic used in both the groups and IOP were recorded after induction, at BIS 40-60, after LMA insertion (Group L), at BIS 60-80 and BIS more than 80. RESULTS: The IOP values did not differ significantly between the groups at BIS 40-60 and at BIS 60-80. Moreover, pre and post LMA insertion IOP values were also comparable in Gr L (p = 0.11). However, significant increase in IOP values were observed with increasing BIS values within each group. The mean IOP in Group M at BIS 40-60 was 13.41 ± 4.04 as compared to 14.18 ± 3.64 at BIS 60-80 (p = 0.003). There was a similar pattern observed in Group L, where mean IOP at BIS 40-60 & BIS 60-80 was 14.13 ± 4.90 and 15.52 ± 4.57 respectively (p < 0.001). CONCLUSION: Either facemask or classic LMA can be safely used as per anaesthesiologist's preference without any significant effect on IOP. BIS monitoring may be used during IOP measurement in paediatric glaucoma suspects for accurate assessment of IOP.

Severity of visual field defects in primary congenital glaucoma and their risk factors.

PURPOSE: The primary objective of the study was to assess the frequency and severity of visual field defects (VFD) in primary congenital glaucoma (PCG). The secondary objective was to ascertain any associated risk factors. METHODS: An ambispective review of patients with PCG on follow-up with a 'target' intraocular pressure (IOP) of ≤ 15 mmHg. Age, sex, laterality, duration of follow-up, baseline IOP, baseline cup-disc ratio (CDR), central corneal thickness (CCT), age during filtering surgery, second surgery if any, yearly IOP, glaucoma medications and best corrected visual acuity from 2013 (year 1) to the final review and final CDR were noted down. Children ≥ 5 years of age with best corrected visual acuity ≥ 6/60 were subjected to manual kinetic Goldmann perimetry, and visual field defects (VFD) were identified. RESULTS: Seventy-one of 90 eyes completed a reliable kinetic perimetry. The mean age of children was 12.34 ± 4.86 years, and the mean follow-up duration was 10.77 ± 4.69 years. Baseline IOP and CDR were 29.07 ± 8.83 mmHg and 0.66 ± 0.22, respectively. 86.67% of eyes underwent a trabeculotomy + trabeculectomy with mitomycin-C. Thirty-one eyes (34.44%) required a second surgery, 25 of which were bleb revisions and 3 trabeculectomies. Mean IOP and CDR during last visit were 10.23 ± 2.76 mmHg and 0.52 ± 0.25, p < 0.001 as compared with baseline. On Goldmann perimetry, 19 eyes, 26.76%, had defects, arcuate scotoma being most frequent. On the Fisher exact test, a baseline/final CDR > 0.8, undergoing just a trabeculectomy with MMC, needing ≥ 2 glaucoma medications on review or a repeat trabeculectomy was associated with greater severity of VFD. On univariate logistic regression, eyes that needed a bleb revision [OR, 95% CI 9.75 (2.66-35.67), p = 0.001], a repeat trabeculectomy with mitomycin-C [OR (CI) 18 (1.31-245.58), p = 0.03] and final CDR of > 0.8 [OR (CI) 23.1 (3.7-144.21), p = 0.001] were associated with VFD. On multivariable regression analysis, female sex [OR (CI) 18 (2.01-161.04), p = 0.01] was identified as the single most important risk factor for development of a VFD. CONCLUSION: At a 'target' IOP of ≤ 15 mmHg, 26.76% of PCG eyes manifested a VFD over 10 years. Baseline and/or final CDR > 0.8, necessity for ≥2 medications or a repeat glaucoma surgery, and female sex were identified as risk factors for development and greater severity of glaucomatous VFD.

Clinical and ASOCT evaluations of 'bleb-sparing epithelial exchange' in paediatric and adult dysfunctional blebs over 5 years.

PURPOSE: To evaluate the long-term outcome of 'bleb-sparing epithelial exchange' surgery for dysfunctional filtering blebs in paediatric and adult eyes. METHODS: Patients who had undergone bleb revision ≥ 5 years back and were on regular follow-up were included. Age, ocular diagnosis, details of primary filtering surgery including mitomycin-C (MMC) usage, indication and year of bleb revision were recorded. After bleb revision, the mean intraocular pressure (IOP), glaucoma medications and best corrected visual acuity (BCVA) up to 5 years were noted. On last review, clinical details, bleb characteristics and swept source anterior segment tomographic (SSOCT) assessment of bleb were recorded. Comparative analysis of paediatric and adult eyes was performed. MAIN OUTCOME MEASURES: Change in IOP and BCVA. 'Complete success' was defined as IOP ≥ 6 to ≤ 18mmHg without use of any topical glaucoma medications and 'Qualified success' when ≥ 1 topical glaucoma medication(s) was required. RESULTS: A total of 51 eyes of 51 consecutive patients were studied, among which 22 were children. The mean duration between filtering surgery and bleb revision was 4.54 ± 1.53 years in paediatric and 6.48 ± 3.5 years in the adult group, p = 0.04. Children underwent trabeculotomy + trabeculectomy with 0.04% MMC, while adults underwent trabeculectomy with 0.02% MMC. The mean pre-revision IOP was 6.38 ± 2.80 and 6.51 ± 2.78 mmHg in the paediatric and adult group respectively, p = 0.86. At 3 months post-revision, it increased to 11.81 ± 3.48 and 12.75 ± 3.52 mmHg respectively (p < 0.001). At final review, mean IOP of paediatric group was 10.90 ± 2.59 and adult group was 11.86 ± 2.66 mmHg, p = 0.20. At 5 years, complete success was 68.18% and 72.41%, and qualified success was 31.87% and 27.59% in the former and latter group respectively, p = 0.49. No failures were seen. Kaplan-Meier probability at 5 years for IOP target ≤ 18, ≤ 15 and ≤ 12 in children was 95.45%, 63.64% and 50% and in adults 93.10%, 65.52% and 41.38% respectively. BCVA improved up to 1 year in paediatric group, with continued improvement in adults up to 3 years. SSOCT measured bleb height was 0.88 ± 0.37 and 1.32 ± 0.49mm in children versus adults (p = 0.006) and wall thickness, 0.35 ± 0.22 and 0.58 ± 0.24mm respectively, p = 0.008. CONCLUSION: Bleb-sparing epithelial exchange is an equally safe and effective technique with good long-term success in both paediatric and adult dysfunctional blebs.

COMPARATIVE EVALUATION OF ANTERIOR SEGMENT OPTICAL COHERENCE TOMOGRAPHY, ULTRASOUND BIOMICROSCOPY, AND INTRAOCULAR PRESSURE CHANGES AFTER PANRETINAL PHOTOCOAGULATION BY PASCAL AND CONVENTIONAL LASER.

PURPOSE: To compare intraocular pressure, anterior segment optical coherence tomography, and ultrasound biomicroscopy parameters over 3 months after panretinal photocoagulation (PRP) for proliferative diabetic retinopathy after 1 of 2 sittings by conventional laser (half PRP) and a single sitting of Pattern Scan Laser (PASCAL) PRP. METHODS: This was a prospective, randomized, interventional study. All tests were performed at baseline, and at 1, 6, and 24 hours, and 1, 4, 8, and 12 weeks after PRP. RESULTS: The intraocular pressure at 1 hour and 6 hours after PRP was significantly raised in both groups. Mean intraocular pressure was 21.17 ± 4.01 mmHg after PASCAL and 17.48 ± 3 mmHg after conventional laser at 1 hour, P < 0.001. On anterior segment optical coherence tomography, conventional laser PRP caused a more significant narrowing of angle-opening distance (AOD750) and trabecular-iris space area (TISA 500), P = 0.03 and 0.04, respectively, on Day 1. Ultrasound biomicroscopy showed a significantly narrow angle in both groups on Day 1. A significant increase in ciliary body thickness was observed in both groups, with 57.1% of PASCAL and 100% of conventionally treated eyes showing ciliary effusion on Day 1 that decreased but persisted for the next 3 months. CONCLUSION: Performing PRP in sittings, prescribing previous glaucoma medications in patients at risk, and recording intraocular pressure an hour after the PRP could decrease complications.

Does TRABECULECTOMY meet the 10-10-10 challenge in PACG, POAG, JOAG and Secondary glaucomas?

PURPOSE: Evaluation of the intraocular pressure (IOP) lowering efficacy of trabeculectomies over > 10 years and their ability to stabilize glaucomatous optic neuropathy. METHODS: In total, 181 eyes (136 patients), which underwent trabeculectomy (10 min surgery) at least 10 years prior and were on regular follow-up, were evaluated. Qualified/complete success was taken as criteria A: IOP ≤ 12 mmHg, B: IOP ≤ 15 mmHg and C: IOP ≤ 18 mmHg, with all > 5 mmHg, with/without medications. Target IOP in advanced glaucoma is about 10 mmHg, therefore trabeculectomy 10-10-10 challenge! RESULTS: The mean age of patients was 46.32 ± 11.50 years. Absolute success was 50.27%, 54.14% and 59.66% according to criteria A, B and C at last follow-up, while qualified success was 70.11%, 81.77% and 96.13%. An IOP of ≤ 12 mmHg was noted in 34, 64.15%, PACG eyes, 14, 73.68%, POAG, 15, 65.22%, JOAG and 64, 74.42%, secondary glaucoma eyes. The reduction in IOP overall was 64.83 ± 16.80% at last review and was 59.47 ± 16.07% in PACG, 62.40 ± 17.72% in POAG, 71.89 ± 8.50% in JOAG and 67.74 ± 18.10% in secondary glaucoma eyes. "Target" IOP was achieved in 97.29% of early glaucoma, 85.71% moderate glaucoma and 70% severe glaucoma eyes. 97.24% of patients were perimetrically stable. 2.21% of eyes post-trabeculectomy had a shallow anterior chamber needing surgical intervention. Visual acuity was maintained or better in 93.92% of patients, with a cataract surgery performed in 6.63% eyes. A repeat trabeculectomy was performed in 3.31% of eyes. CONCLUSION: Trabeculectomy 10-10-10 is achievable in the long term, with few complications or repeat surgical interventions in the majority of POAG, PACG, JOAG and secondary glaucomas. Therefore, trabeculectomy should not be relegated to a last resort, but should be undertaken as soon as possible, if medical therapy is inadequate, unaffordable or compliance is an issue.

Effect of Ultra-Small Chitosan Nanoparticles Doped with Brimonidine on the Ultra-Structure of the Trabecular Meshwork of Glaucoma Patients.

Brimonidine, an anti-glaucoma medicine, acts as an adrenergic agonist which decreases the synthesis of aqueous humour and increases the amount of drainage through Schlemm's canal and trabecular meshwork, but shows dose-dependent (0.2% solution thrice daily) toxicity. To reduce the side effects and improve the efficacy, brimonidine was nanoencapsulated on ultra-small-sized chitosan nanoparticles (nanobrimonidine) (28 ± 4 nm) with 39% encapsulation efficiency, monodispersity, freeze-thawing capability, storage stability, and 2% drug loading capacity. This nanocomplex showed burst, half, and complete release at 0.5, 45, and 100 h, respectively. Nanobrimonidine did not show any in vitro toxicity and was taken up by caveolae-mediated endocytosis. The nanobrimonidine-treated trabeculectomy tissue of glaucoma patients showed better dilation of the trabecular meshwork under the electron microscope. This is direct evidence for better bioavailability of nanobrimonidine after topical administration. Thus, the developed nanobrimonidine has the potential to improve the efficacy, reduce dosage and frequency, and improve delivery to the anterior chamber of the eye.

Long-term evaluation of ocular hypertension with primary angle closure and primary open angles.

PURPOSE: To evaluate the long-term course of primary angle-closure ocular hypertension and primary open-angle ocular hypertension and possible risk factors for progression to glaucoma. METHODS: A total of 109 eyes of 109 ocular hypertension (OHT) patients with a minimum follow-up period of 5 years having complete ocular/medical records were evaluated. They were classified into primary angle closure or primary open angle based on gonioscopy at baseline. Baseline and review data of Humphrey field analyser, HFA, and Heidelberg retinal tomography, HRT, were recorded. Guided progression analysis (GPA) and univariate Cox regression were used for time to event analysis in identifying progression to glaucoma. RESULTS: Over a mean follow-up of 12.18 ± 4.8 years, progression to glaucoma was 17.43% (19 eyes), out of whom 5.5% (6 eyes) showed ≥ 3 loci on GPA. Sub-classifying them, progression to primary angle-closure glaucoma was 19.72%, and that of primary open-angle glaucoma was 13.16%. The mean time to progression was 9.34 ± 3.6 years. Significant risk factors included small disc area (≤ 1.99 sq.mm on HRT), requirement of ≥ 2 drugs to maintain target IOP and those engaged in activities yielding a Valsalva effect in daily life. Coronary artery disease (CAD) and systemic use of steroids were associated with increased severity. CONCLUSION: Overall progression of OHT to glaucoma was 17.43% over a mean of 9 years, with target IOP of ≤ 18 mm Hg. Patients with smaller discs, CAD, exercising Valsalva type activities and using ≥ 2 glaucoma medications or systemic steroids should be closely monitored.

Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

Is combined mechanism glaucoma a distinct entity?

PURPOSE: Primary adult glaucomas that have an occludable angle with peripheral anterior synechiae which are too few to account for the chronically raised IOP, or the glaucomatous optic neuropathy, do not fit the definition of either POAG or PACG and can be considered as combined mechanism glaucoma (CMG). We aimed to compare the clinical features and anatomical parameters of combined mechanism glaucoma with age, sex, and refraction-matched POAG and chronic PACG eyes. METHODS: Consecutive adult patients with definitive optic nerve head and perimetric changes of glaucoma were screened at a tertiary care center. All glaucomatous eyes having an IOP > 22 mmHg on at least three separate occasions and glaucomatous optic neuropathy consistent with moderate visual field loss in the eye were divided as POAG, PACG, and CMG. Eyes with occludable angles having < 90° of goniosynechiae were diagnosed as CMG. A detailed clinical examination, ocular biometry, and ASOCT were performed in the better eye of all individuals. RESULTS: A total of 93 patients with similar visual field index or pattern standard deviation on perimetry were evaluated: 32 POAG, 31 CMG, and 30 PACG. The mean anterior chamber depth was 3.47 ± 0.37 mm in POAG, 2.81 ± 0.32 mm in PACG, and 3.06 ± 0.26 mm in CMG (p < 0.0001). Mean lens thickness was 4.22 ± 0.27 mm in POAG, 4.53 ± 0.35 mm in PACG, and 4.44 ± 0.29 mm in CMG (p = 0.0004). Iridotrabecular contact on ASOCT was nil in POAG, a mean of 87.60 ± 12.802% in PACG eyes, and 15.23 ± 14.19% in CMG eyes, p < 0.0001. CMG was similar to PACG in terms of corneal diameters and lens thickness and had an axial length in between PACG and POAG. On ASOCT, all parameters had highest values in POAG eyes and the least in PACG eyes, with CMG eyes having values in between the other two groups, p value of < 0.0001 between each group for all parameters. CONCLUSION: This study has demonstrated significantly different anatomical parameters in eyes with CMG, in addition to the differences on gonioscopy and iridotrabecular contact, indicating that CMG is discernibly dissimilar to PACG and POAG.

Transscleral Suture-Fixated Versus Intrascleral Haptic-Fixated Intraocular Lens: A Comparative Study.

PURPOSE: To compare the clinical outcomes between sutured transscleral-fixated and intrascleral haptic-fixated posterior chamber intraocular lens (IOL). SETTING: Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi. DESIGN: A comparative case series. METHODS: Forty eyes of 40 patients were included; 20 in each group. Patients in group 1 underwent sutured transscleral-fixated IOL and those in group 2 underwent intrascleral haptic-fixated IOL augmented by fibrin glue. Parameters evaluated were uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), IOL tilt on ultrasound biomicroscopy (UBM), and pseudophakodonesis on slitlamp and UBM. RESULTS: The most common cause of aphakia was complicated cataract surgery (50%). The mean preoperative UCVA in logarithm of minimum angle of resolution (logMAR) was 1.59±0.24 and 1.63±0.26 in group 1 and 2, respectively (P=0.45). There was significant improvement in UCVA in both groups (P=0.001) at 6 months (group 1: 0.33±0.17; group 2: 0.22±0.10); the improvement being greater in group 2 (P<0.05). Mean percentage endothelial cell loss and IOP change were comparable. Mean CMT (µm) was 250.95±23.98 and 225.85±21.13 in group 1 and 2, respectively (P=0.009). Pseudophakodonesis was more in group 1 as assessed on slitlamp (P=0.037) and as assessed on UBM (P=0.046). Macular edema was the most common complication seen more in group 1. CONCLUSIONS: Intrascleral haptic-fixated IOL provides more stable fixation, better visual outcome, and lesser complication in comparison with sutured transscleral-fixated IOL.

Evaluation of physical properties and dose equivalency of generic versus branded latanoprost formulations.

The purpose of this study was to comparatively evaluate the pharmaceutical characteristics of various marketed generic formulations of prostaglandin analogue latanoprost in the Indian market. Three generics of latanoprost and one branded (Xalatan) formulation (five vials each) were obtained from authorized agents from the respective commercial sourcing having the same batch number. These formulations were coded, and the labels were removed. At a standardized room temperature of 25 °C, the concentration, osmolarity, drop size, pH, and total drops per vial were determined for Xalatan and all the generics of latanoprost. The concentration of various brands varied between 50.49 ± 0.36 and 58.90 ± 0.52 µg/ml as compared to the standard labeled concentration of 50 µg/ml on the latanoprost vials. The concentration of drugs in individual drop varied from 1.30 ± 0.05 to 1.78 ± 0.04 µg/drop. The volume of drug formulation per bottle varied from 2.4 ± 0.12 to 2.6 ± 0.09 ml/bottle. The number of drops per bottle varied from minimum of 88.60 ± 0.10 drops to maximum of 102.0 ± 4.3 drops across all the formulations, while the drop size varied from 25.72 ± 2.70 to 29.97 ± 1.38 µl. The osmolarity of 2/4 drugs was within 300 mOs M (±10 %). The specific gravity varied between 0.98 ± 0.01 and 1.007 ± 0.01, while pH was between 7.05 ± 0.004 and 7.13 ± 0.005. Two of the generic brands were outside the United States pharmacopoeia limits (±10%) for ophthalmic formulation, with concentration exceeding the limits by 3 % (p = 0.151) and 8 % (p = 0.008), respectively. This pilot study highlights that there are significant variations in the drug concentrations and physical properties of generic latanoprost formulations. Although none of the brands had concentrations below the recommended level, two of the brands had concentrations exceeding the limits by 3 and 8 %, respectively.

Functional evaluation of an iridotomy in primary angle closure eyes.

OBJECTIVE: To evaluate the functional efficacy of an iridotomy in primary angle closure (PAC) eyes by measuring IOP responses to provocative tests before and after iridotomy. DESIGN: Prospective cohort study. SUBJECTS: 50 consecutive adult patients, 40-60 years of age, having primary angle closure. METHODS: Clinical examination, perimetry, biometry and ultrasound biomicroscopy of the angle were done. A darkroom prone provocative test (DRPPT), a mydriatic test and a Valsalva maneuver were performed before and after the iridotomy. MAIN OUTCOME MEASURES: IOP change in response to the provocative tests before and after iridotomy, and correlation with baseline parameters. RESULTS: IOP at baseline and after iridotomy was 14.4 ± 2.7 mmHg and 14.3 ± 2.6 mmHg, respectively (p = 0.)83. There was no significant change on diurnal phasing before and after an iridotomy (p = 0.)11. The mean IOP rise was 5.9 ± 3.7 mmHg on the DRPPT, 4.3 ± 3.5 mmHg on the Mydriatic test and 9.1 ± 4.9 mmHg on the Valsalva maneuver, and was reduced significantly to 3.2 ± 2.1 mmHg, 2.3 ± 1.8 and 6.4 ± 3.5, respectively(p < 0.001 for all tests). The decrease in pupillary block component for all 50 eyes was 46.5 % for the mydriatic test, 45.8 % for the DRPPT and 29.7 % for the Valsalva maneuver. PAC eyes positive on the DRPPT and mydriatic test prior to an iridotomy became negative after laser iridotomy in 75.9 and 84.6 % eyes, respectively, but on the Valsalva maneuver, only 23.8 % became negative. After iridotomy, eyes that continued to be positive on the mydriatic test had a significantly thicker lens (p = 0.02), decreased TCPD (p = 0.014) and narrower trabecular-iris angle (p = 0.048). On the DRPPT, they had a thicker lens (p = 0.03), shorter iris thickness (p = 0.025) and TCPD (p = 0.032), and on the Valsalva maneuver, they had a narrower scleral-ciliary process angle (SCPA; p = 0.019) and shorter TCPD (p = 0.015). CONCLUSIONS: This comprehensive functional evaluation of laser iridotomy in early PAC eyes showed a significant reduction in the pupillary block component of IOP response to provocative testing, possibly decreasing IOP fluctuations over time. An iridotomy does not, however, significantly change mean IOP or diurnal phasing of IOP in PAC eyes. Eyes with a very narrow angle or a thick lens may continue to have angle closure due to other pathomechanisms for angle closure.

Risk factors for intra-operative complications during phacoemulsification performed by residents.

The purpose of this study was to determine the risk factors for occurrence of intra-operative complications during phacoemulsification performed by residents. One hundred fifty patients with cataract who underwent phacoemulsification by residents, with an experience of five or more phacoemulsification surgery, at a tertiary care centre were included in this study. The pre-operative data of these patients were collected from the hospital records. Surgeons were interviewed immediately after the surgery regarding the surgeon experience, phacoemulsification technique, machine factors, and intra-operative complications. Statistical analysis was done to determine pre-operative and intra-operative risk factors. The overall surgical complication rate in resident-performed phacoemulsification was 37 % of which major and minor complications were 21 and 16 %, respectively. Success in terms of placement of intraocular lens in capsular bag was 84 %. The most common major and minor complications found were posterior capsular tear and irregular capsulorhexis, respectively. Systemic and ocular features of patients as well as type of machine (longitudinal versus torsional longitudinal) had no significant association in terms of complication rate. Increase in success rate was seen with increase in semester and number of surgeries performed. Patient factors including general physical condition, systemic diseases, and anatomical factors do not influence success in resident-performed phacoemulsification. With increase in semester of residents, there is a significant decrease in intra-operative complications. Minor complications in the beginning of case lead to increase in major complications later on during the case and decrease in success rate by junior-semester residents.

Agreement between diurnal variations of intraocular pressure by Tono-Pen and Goldmann applanation tonometer in patients on topical anti-glaucoma medication.

To estimate agreement in diurnal variations of intraocular pressure (IOP) by Tono-Pen (TP) and Goldmann applanation tonometer (GAT) in glaucoma patients on topical anti-glaucoma medication(s). IOP was measured at every 3 h from 7 a.m. to 10 a.m. in 50 eyes of glaucoma patients on topical medication(s). Diurnal fluctuation of IOP by each method was calculated as maximum-minimum IOP in a day. Central corneal thickness (CCT) was measured by ultrasonic pachymeter. There was good correlation between TP and GAT at all times during a day, minimum, and maximum IOPs during a day (Correlation coefficient, 0.706 at 7 a.m., 0.624 at 10 a.m., 0.682 at 1 p.m., 0.814 at 4 p.m., 0.652 at 7 p.m., 0.572 at 10 p.m., 0.668 minimum IOP, 0.689 maximum IOP). Mean IOPs by TP were always higher than GAT at all times during a day. Bland-Altman plots suggested a close relationship between the two sets of readings, and that this relationship was consistent at different times in a day, in maximum IOPs, minimum IOPs and also in fluctuation of IOPs. Linear regression analysis between the differences of diurnal fluctuation (diurnal fluctuation by GAT-diurnal fluctuation by TP) and CCT showed strong association (R 2 = 0.857, p < 0.001). The mean change in difference of diurnal fluctuation (GAT-TP) for a 10-micron increase in CCT was 0.69 mmHg. TP can be considered a reliable alternative to GAT in glaucoma patients for knowing the diurnal control of IOP; however these two methods should not be used interchangeably. Difference of diurnal fluctuation between two methods is dependent on CCT.

Spinocerebellar ataxia 7 (SCA7) in Indian population: predilection of ATXN7-CAG expansion mutation in an ethnic population.

BACKGROUND & OBJECTIVES: Spinocerebellar ataxia 7 (SCA7) is a rare form of neurodegenerative disorder with the clinical manifestation of cerebellar ataxia and retinal degeneration. In this study we describe the clinico-genetic characteristics of nine SCA7 families of Indian origin and cross compare these with other available worldwide studies. METHODS: Thirty five individuals from nine SCA7 families were clinico-genetically characterized and CAG repeat distribution analysis was carried out in 382 control DNA samples from healthy controls (derived from 21 diverse Indian populations based on ethnic and linguistic and geographical location). RESULTS: Of the nine families studied, 22 affected individuals and one asymptomatic carrier were identified. The average age at disease onset was 23.4±12.6 yr. The length of expanded CAG ranged from 40-94 with mean value of 53.2±13.9. The main clinical findings in affecteds individuals included cerebellar ataxia, and retinal degeneration along with hyper-reflexia (95%), slow saccades (85%) and spasticity (45%). Analysis of the association of number of CAG repeats with disease onset revealed that <49 repeats were associated with earlier age at onset in South East Asians compared to European populations. Further analysis of CAG repeats from 21 diverse Indian populations showed pre-mutable repeats (28-34) alleles in the IE-N-LP2 population. Six of the nine families identified in this study belonged to the same ethnic population. INTERPRETATIONS & CONCLUSION: Our results show that presenece of SCA7 is relatively rare and confined to one ethnic group from Haryana region of India. We observed a homogeneous phenotypic expression of SCA7 mutation as described earlier and an earlier age of onset in our patients with CAG <49. The identification of pre-mutable allele in IE-N-LP2 suggests this population to be at the risk of SCA7.