Case Report: Pediatric Ocular Ischemia and Neovascular Glaucoma in Neurofibromatosis Type 1.

SIGNIFICANCE: Neovascular glaucoma is an important subset of secondary glaucoma in neurofibromatosis patients. Vasculopathy of the ophthalmic circulation needs to be borne in mind while evaluating their etiology. PURPOSE: This study aimed to report the presentation, diagnostic work-up and management of an unusual case of neovascular glaucoma in a child. CASE REPORT: A 7-year-old boy presented with uniocular ischemic fundus and secondary neovascular glaucoma. Detailed family history and evaluation led to a diagnosis of familial neurofibromatosis type 1. Fundus fluorescein angiography revealed compromised retinal and choroidal circulations in the affected eye. Ocular ultrasound B scan and neuroimaging did not show any contributory lesions. Cardiovascular evaluation was within normal limits. Ophthalmic Doppler imaging revealed normal proximal ophthalmic arteries in both eyes; however, the central retinal artery of the affected eye showed low flow in its proximal part and absent flow in the distal part, as compared with the fellow eye showing regular flow until the optic disc margin. Corroborating the clinical, fundus fluorescein angiography and Doppler findings, a diagnosis of neurofibromatosis type 1-related vasculopathy of the distal ophthalmic artery was made. Poor visual prognosis for the affected eye was explained, and anterior retinal cryopexy along with cyclocryotherapy was performed to treat the neovascular glaucoma. CONCLUSIONS: Vasculopathy of the ophthalmic circulation is an important cause of neovascular glaucoma in neurofibromatosis patients. The morphology of Lisch nodules may be altered in an ischemic eye, and therefore, careful examination of the other eye and systemic evaluation is vital in such unusual scenarios.

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.

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.

Possible role of differentially expressing novel protein markers (ligatin and fibulin-7) in human aqueous humor and trabecular meshwork tissue in glaucoma progression.

The pathological mechanism underlying glaucoma has always been a complex aspect of this permanently blinding disease but proteomic studies have been helpful in elucidating it to a great extent in several studies. This study was designed to evaluate the expression and to get an idea about the function of two novel markers (ligatin and fibulin-7) identified in human aqueous humor (hAH) in relation to glaucomatous progression. A significant increase in the protein content of glaucomatous hAH compared to that of non-glaucomatous controls (NG-Ctrls) was observed. Ligatin, fibulin-7, and its proteolysis were revealed in hAH of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG) and NG-Ctrls. Quantification confirmed no significant difference in expression of ligatin, whereas fibulin-7 was significantly (P < 0.05) low in hAH of PACG in comparison to NG-Ctrls and POAG. Importantly the immunohistochemical assay for both indicated their possible involvement in the maintenance of the appropriate structure of TM in vivo. Since oxidative stress is a major contributor to glaucomatous pathogenesis, in vitro analysis of nuclear and cytoplasmic fractions indicated intracellular changes in localization and expression of ligatin upon oxidative insult of human trabecular meshwork (TM) cells. While no such changes were found for fibulin-7 expression. This was also corroborated with the immunocytochemical assay. Though a study with a small sample size, this is the first report which confirms the presence of ligatin and fibulin-7 in hAH, quantified their differential expression, and indicated the possibility of their involvement in the maintenance of the TM structure.

Comparative evaluation of the aqueous humor proteome of primary angle closure and primary open angle glaucomas and age-related cataract eyes.

PURPOSE: To analyze and compare the total proteome of aqueous humor (AH) from patients having primary angle closure glaucoma (PACG), primary open angle glaucoma (POAG) and age-related cataract. MATERIALS AND METHODOLOGY: Aqueous humor was collected from age-matched PACG, POAG and cataract patients who underwent surgery, and it was immediately stored at - 80 °C until analysis. From each sample, 25 µg of total protein was subjected to trypsin digestion and subsequently LC-MS/MS analysis was performed for the deep proteome analysis. The data acquired after the LC-MS/MS analysis were analyzed using Proteome Discoverer 1.4. The identified peptide matches were validated using percolator, at less than 1% false discovery rates. RESULTS: A total of 625, 594 and 636 proteins were identified in PACG, POAG and cataract groups, respectively (n = 9 in each group). The inter-group comparison among all these groups showed that 246 proteins were identified in all the three groups. An average of 236 ± 42, 218 ± 40 and 214 ± 62 proteins from each AH sample of PACG, POAG and cataract, respectively, was identified. There were 53 proteins commonly found in all 9 PACG AH, 59 proteins in POAG AH and 42 proteins in 9 cataracts AH samples. In the individual analysis, there were 28 proteins found in all the samples analyzed representing the "constitutive AH proteome." Spectral counting analysis of 246 proteins identified in all three group types showed significant differences in protein abundance. In proteins unique to PACG AH, 7 proteins viz. ARHGEF12, APC2, WAS, PIK3CG, ITGB1, MSN and PFN1 out of 226 were found in "Regulation of Actin Cytoskeleton" pathway, whereas in POAG 5 out of 206 proteins viz. ADCY2, ITPR1, MAPK3, MAP3K2 and TUBB1 were found in "Gap Junction" pathway. CONCLUSIONS: A qualitative as well as a quantitative comparison of proteomes of AH from PACG, POAG and age-related cataract eyes showed significant differences, thus providing clues to the disease pathophysiology.

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.

Effect of intracameral human cord blood-derived stem cells on lasered rabbit trabecular meshwork.

BACKGROUND: This study aimed to investigate the effect of intracameral human cord blood stem cells on lasered rabbit trabecular meshwork. METHODS: Immediately following diode laser application to the trabecular meshwork, human cord blood stem cells were injected intracamerally, in one eye of 12 albino rabbits. The other eye of ten rabbits was lasered controls and two eyes were normal controls. Rabbits were killed after 4, 8 and 12 weeks. RESULTS: Lasered control rabbit eyes showed significant disruption of trabecular architecture, loss and pleomorphism of trabecular endothelial cells and progressive narrowing of trabecular spaces till 12 weeks. In contrast, lasered eyes, concurrently injected with human cord blood stem cells, showed relatively preserved endothelial cellularity and structure of the trabecular meshwork, at all time points. Human CD34- and CD44-positive cells were identified in 7/8 eyes treated with stem cells, at 4 and 8 weeks, and 2 of 3 at 12 weeks. Many PKH26-labeled human cord blood cells were visible throughout the trabecular area at 4 weeks. They gradually decreased in number by 8 weeks, and at 12 weeks, they appeared to be oriented along trabecular beams. CONCLUSIONS: There was a relative preservation of cellularity and architecture of the trabecular meshwork in eyes injected with human cord blood stem cells, as compared to lasered control eyes up to 12 weeks, without significant inflammation. This suggests a probable role for such stem cells in eyes with glaucoma, having trabecular dysfunction.

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.

Genetic variants associated with primary open angle glaucoma in Indian population.

Glaucoma is a very common disorder of the eye wherein the disturbance of the structural or functional integrity of the optic nerve causes characteristic atrophic changes in the optic nerve, which may lead to specific visual field defects over time. Primary open angle glaucoma (POAG) is most frequent among the three principle glaucoma subtypes. With well-established role of genes like Myocilin (MYOC), Optineurin (OPTN) and WD repeat Domain 36, (WDR36), at least 29 genetic loci have been found till date to be linked to POAG. Moreover, association studies have found 66 loci with 76 genes associated to POAG till date with conflicting results. This particular study is to summarize the current knowledge regarding the change in glaucoma prevalence worldwide and in India from 1993 onwards and compiles all the studied genes that are involved in POAG pathogenesis in Indian population.

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.

Corneal changes in childhood glaucoma.

OBJECTIVE: To study the clinical features and topography of the cornea in eyes with childhood glaucoma. DESIGN: Cross-sectional, observational study. PARTICIPANTS: Fifty-eight eyes with childhood glaucoma and 28 eyes of age-matched controls. METHODS: Clinical and topographic corneal changes were evaluated. MAIN OUTCOME MEASURES: Corneal topographic changes were evaluated on Orbscan (Orbscan Topography System II; Bausch & Lomb, Salt Lake City, UT) in eyes with childhood glaucoma and those changes were compared with the control eyes. RESULTS: Fifty-eight eyes with childhood glaucoma and 28 eyes of age-matched controls were evaluated. Thirty-six eyes (62.1%) were classified as having primary childhood glaucoma and 22 eyes (37.94%) as having childhood glaucoma with associated ocular anomalies. The corneas in 18 of 58 eyes (31.0%) with childhood glaucoma were clear, whereas 24.1% of eyes (14/58 eyes) had some corneal opacification. Haab's striae were noted in 44.8% of eyes (26/58 eyes) and were most frequently present between 3 and 5 mm from the optical axis. The mean posterior elevation recorded in eyes with childhood glaucoma controlled with medication or surgery was significantly higher than that in control eyes: 0.043 ± 0.027, 0.042 ± 0.017, and 0.018 ± 0.058 µm, respectively (P < 0.0001). The presence of Haab's striae was correlated significantly with a higher posterior elevation (P = 0.0396) and poor vision. The mean anterior elevation in eyes with childhood glaucoma (0.022 ± 0.015 µm) and in control eyes (0.015 ± 0.078 µm) was comparable (P = 0.08). Corneal astigmatism in eyes with childhood glaucoma was significantly higher and irregular compared with that in control eyes: 2.09 ± 1.40 versus 0.93 ± 0.60 diopter cylinder (P = 0.0001); the irregularity index was 2.8 (range, 1-18.1) and 2.3 (range, 0.6-2.3) at 3 mm (P = 0.0005) and 3.2 (range, 1.4-21.3) and 1.8 (range, 0.5-2.9) at 5 mm, respectively (P = 0.0003). Best-corrected visual acuity correlated significantly with cup-to-disc ratio, axial length, refractive error, astigmatism, and posterior corneal elevation. Multivariate analysis showed a significant correlation only with cup-to-disc ratio and axial length. CONCLUSIONS: Childhood glaucoma causes a significant increase in posterior corneal elevation and irregular astigmatism, which contribute to visual disability in such eyes.

Evaluating the long-term efficacy of short-duration 0.1 mg/ml and 0.2 mg/ml MMC in primary trabeculectomy for primary adult glaucoma.

OBJECTIVE: To evaluate safety and efficacy of 0.1 mg/ml versus 0.2 mg/ml mitomycin-C (MMC), applied for 1 min subconjunctivally, during trabeculectomy for primary adult glaucoma in previously un-operated eyes. MATERIALS AND METHODS: This is a randomised controlled, non-inferior, clinical trial consisting of 50 consecutive POAG or CPACG patients uncontrolled on maximal hypotensive therapy, meeting all inclusion criteria. Patients were randomized into two groups and underwent a standard limbus-based trabeculectomy with MMC: Group I, 0.1 mg/ml and Group II, 0.2 mg/ml. The pre-operative and post-operative intraocular pressure (IOP), bleb morphology, and visual acuity were recorded every 6 months for 2 years. Complete success (primary outcome) was defined as IOP ≤ 15 mmHg without any additional medications at the end of 2 years. RESULTS: The average age of patients was 62.6 ± 9.8 years and 61.2 ± 8.1 years in Group 1 and 2, respectively; p = 0.57. The mean preoperative IOP was 22.5 ± 1.4 mmHg and 23.3 ± 1.8 mmHg; p = 0.10. The mean IOP at 2 years was 11.1 ± 1.6 mmHg and 10.8 ± 2.8 mmHg, a mean reduction in IOP of 50.6 ± 1.23 %, and 53.7 ± 2.25 % in Group I and II, respectively. The complete success was 92.0 % and 91.7 % in the two groups, respectively (p = 0.99), and there was one failure (Group II, post trauma). A wider bleb extent and larger areas of thin, transparent conjunctiva over the bleb were seen with the 0.2 mg/ml MMC group (p < 0.001) and in PACG eyes; p < 0.04. CONCLUSION: A 1-min subconjunctival application of low dose 0.1 mg/ml MMC is non-inferior to 0.2 mg/ml and is probably a safer alternative, as thinning of the bleb is significantly less frequent in the long term.

Risk of perimetric blindness among juvenile glaucoma patients.

AIM: To estimate rates of progression and to asssess the projected lifetime risk of blindness among treated eyes of juvenile-onset primary open glaucoma (JOAG) patients. METHODS: Rates of change of the visual field index of JOAG patients (diagnosed between the age of 10-40 years), with at least 5 year follow up, were used to estimate the lifetime risk of perimetric blindness. Both the eyes of patients were included in the analysis wherever possible. Average life expectancy of the population was used to calculate the lifetime risk of perimetric blindness. A regression analysis of factors contributing to faster rates of progression was performed. RESULTS: One hundred and two eyes of 54 patients were included in the study. Mean age at the time of baseline visual field was 26.6 ± 9.8 years (15-40 years). The average visual field index change per year was -0.9% (range -6.4 to +2.0% per year) and 18 eyes (17%) showed a progression greater than -2% per year. The cumulative risk of an eye losing 50% and 100% of its visual field index was 30% and 22% respectively over the patients' lifetime. The projected risk of bilateral blindness among JOAG patients over their lifetime was 10%. Long term IOP fluctuation was significantly associated with faster rates of progression (Odds ratio = 2.74; p = 0.012). CONCLUSIONS: Though the rate of visual field deterioration with treatment, among juvenile glaucoma patients is lower compared to that among other types of primary glaucoma, the projected lifetime risk of perimetric blindness in these eyes is similar, despite the longer duration of disease in this age group.

IOP agreement between I-Care TA01 rebound tonometer and the Goldmann applanation tonometer in eyes with and without glaucoma.

To analyze correlation of intraocular pressure (IOP) measurement between new rebound tonometer (RBT) I-Care TA01 and Goldmann applanation tonometer (GAT). One hundred eighty-five eyes of 185 subjects presenting with glaucoma or cataract were enrolled in the study. In all patients, IOP was obtained by an ophthalmologist using I-Care TA01 and GAT. IOP between the two were compared at range of 8-15, 16-21, and >22 mmHg and difference was considered as significant at p < 0.05 (t test). Bland-Altman analysis tested agreement between instruments overall and for each subgroup of patients with glaucoma or no glaucoma (cataract only). Of 185 patients, 86 had glaucoma; 99 did not. Mean age of patients was 55.77 ± 14.46 years; with no difference between the two subgroups (p = 0.12). There was no significant difference in mean IOP between the two tonometers at IOP between 8-15 mmHg (p = 0.097) and 16-21 mmHg (p = 0.51). However, a significant difference was observed between the two at IOP > 22 mmHg (p = 0.023) with mean GAT (24.8 mmHg) being higher than mean RBT (23.16 mmHg). Overall, there was no difference between the two (p = 0.59) and they had a high correlation (Pearson correlation r = 0.815; p = 0.01). The mean difference between the two was 0.1 (95 % agreement limits: UL +6 (1.96SD), LL -5.8 (-1.96SD)), in patients with no glaucoma was 0.091 (95 % AL: UL +4.8 (1.96SD), LL -4.6 (-1.96SD)), and in patients with glaucoma was 0.151 (95 % AL: UL +7.25 (1.96SD), LL -6.9 (-1.96SD)). RBT I-Care TA01 and Goldmann tonometer cannot be used interchangeably due to large limits of agreement.