The mutational spectrum of Myocilin gene among familial versus sporadic cases of Juvenile onset open angle glaucoma.

PURPOSE: Juvenile onset primary open angle glaucoma (JOAG) is a rare disorder associated with high IOP and progressive optic neuropathy in patients diagnosed before the age of 40 years. While in some populations it has primarily an autosomal dominant pattern of inheritance, in others it occurs in a primarily sporadic form. The main aim of the study was to assess the relative prevalence of Myocilin (MYOC) mutations in familial versus sporadic cases of JOAG. METHODS: We screened 92 unrelated (sporadic) JOAG patients, and 22 affected families (70 affected members and 36 unaffected) for variations in the MYOC gene. We also analyzed the clinical features associated with these variations. RESULTS: Three coding sequence variants were identified as mutations causing JOAG. Four families segregated distinct mutations at Gly367Arg, and two families at Gln337Arg, while only two sporadic JOAG cases harbored MYOC mutations (Gly367Arg and Gln48His). The frequency of MYOC mutations in familial cases (27%) was significantly higher than in sporadic JOAG cases (2%); p = 0.001. A 90% penetrance for the Gly367Arg variant was seen by the age of 40 years in our patients. Characteristic allele signatures, indicative of specific founder effects, were not observed for the Gly367Arg mutation that was looked for in 12 patients among 2 geographically close families, which harbored this mutation. CONCLUSION: Our data demonstrated that genetic screening for MYOC mutations should be focused toward cases with familial rather than sporadically occurring JOAG.

Differences in outflow channels between two eyes of unilateral primary congenital glaucoma.

PURPOSE: Primary congenital glaucoma (PCG) occurs in only one eye in some patients. We aimed to characterize anatomical features of the angle and Schlemm's canal (SC) in vivo among fellow eyes of patients with unilateral primary congenital glaucoma. METHODS: Both eyes of 33 children with unilateral PCG and 30 healthy, age-matched children, old enough to co-operate were analysed using high-resolution anterior segment spectral domain (SD) OCT. Subgroup analysis was done for the presence/absence of angle dysgenesis as defined by the presence of abnormal tissue/hyper-reflective membrane within angle recess and/or the absence of SC. Other anatomical landmarks differentiating the fellow eyes from eyes with glaucoma were also evaluated and compared with healthy subjects. RESULTS: The presence of abnormal tissue at the angle and/or a hyper-reflective membranous structure covering the meshwork was seen in all affected PCG eyes (100%) and in 21 (63%) unaffected fellow eyes; p = 0.001. The SC could be seen in 8 (24%) affected in comparison with 29 (88%) fellow unaffected eyes; p = 0.001. The ASOCT scans of 54 (90%) healthy eyes and 3 (9%) fellow PCG eyes revealed a direct communication of anterior portion of the SC with the anterior chamber. Among the fellow eyes, a communication of the supraciliary space with anterior chamber could be discerned in 26 eyes (79%). CONCLUSIONS: Despite angle dysgenesis, outflow channels such as the uveoscleral or a direct communication of SC with the anterior chamber play a role in preventing the development of glaucoma in fellow eyes of unilateral PCG.

Long-term functional outcomes of different subtypes of primary congenital glaucoma.

AIM: To analyse long-term visual outcomes across different subtypes of primary congenital glaucoma (PCG). METHODS: Patients with PCG with a minimum of 5-year follow-up post surgery were included in the study. Snellen visual acuity recordings taken at their last follow-up were analysed. We evaluated the results using Kaplan-Meier curves to predict the probability of maintaining good vision (as defined by a visual acuity of 6/18 or better) in our patients after 30-year follow-up. The results were also analysed to determine whether there were any differences in the long-term visual acuities with time between the neonatal and infantile PCG. We also analysed the reasons for poor visual outcomes. RESULTS: We assessed a cohort of 140 patients with PCG (235 eyes) with an average follow-up of 127±62.8 months (range 60-400 months). Overall, the proportion of eyes with good visual acuity was 89 (37.9%), those with fair visual acuity between 6/60 and 6/18 was 41 (17.4%), and those with poor visual acuity (≤6/60) was 105 (44.7%). We found a significant difference (p=0.047) between neonatal and infantile patients with PCG whereby the neonatal cohort fared worse off in terms of visual morbidity. On Kaplan-Meier analysis, the cumulative probability of survival of a visual acuity of 6/18 or better was more among the infantile PCG in comparison to the neonatal PCG (p=0.039) eyes, and more among the bilateral than the unilateral affected eyes (p=0.029). Amblyopia was the most important cause for poor visual acuity as shown on a Cox proportional-hazards regression model. CONCLUSIONS: Long-term visual outcomes of infantile are better than neonatal PCG. Eyes with unilateral have worse visual outcomes compared with those with bilateral PCG because of the development of dense amblyopia.

A Novel Mathematical Model of Glaucoma Pathogenesis.

BACKGROUND: Conventional experimental approaches to understand glaucoma etiology and pathogenesis and, consequently, predict its course of progression have not seen much success due to the involvement of numerous molecular, cellular, and other moieties. An overwhelming number of these moieties at different levels combined with numerous environmental factors further complicate the intricacy. Interaction patterns between these factors are important to understand yet difficult to probe with conservative experimental approaches. METHODS: We performed a system-level analysis with mathematical modeling by developing and analyzing rate equations with respect to the cellular events in glaucoma pathogenesis. Twenty-two events were enlisted from the literature survey and were analyzed in terms of the sensitivity coefficient of retinal ganglion cells. A separate rate equation was developed for cellular stress also. The results were analyzed with respect to time, and the time course of the events with respect to various cellular moieties was analyzed. RESULTS: Our results suggest that microglia activation is among the earliest events in glaucoma pathogenesis. This modeling method yields a wealth of useful information which may serve as an important guide to better understand glaucoma pathogenesis and design experimental approaches and also identify useful diagnostic/predictive methods and important therapeutic targets. CONCLUSION: We here report the first mathematical model for glaucoma pathogenesis which provides important insight into the sensitivity coefficient and glia-mediated pathology of glaucoma. HOW TO CITE THIS ARTICLE: Faiq MA, Sidhu T, et al. A Novel Mathematical Model of Glaucoma Pathogenesis. J Curr Glaucoma Pract 2019; 13(1):3-8.

Merits of trabeculectomy in advanced and end-stage glaucoma.

OBJECTIVES: The aim of the study was to evaluate intraocular pressure (IOP) control, potential benefits, and associated complications in advanced cases of glaucoma (visual acuity of <6/60) after trabeculectomy. Although many studies of trabeculectomy in glaucoma patients have been done, very few in such advanced cases. METHODS: The study was done on 60 cases of advanced primary open-angle glaucoma (POAG). Trabeculectomy was done and IOP control was assessed. Pre-operative workup included a detailed history, slit lamp biomicroscopy, Goldmann applanation tonometry, gonioscopy using Goldmann 2 mirror lens, and detailed fundus examination with the 78D lens. All the patients were to undergo optical coherence tomography and Humphrey automated perimetry. RESULTS: Out of 60 patients with POAG, 48 were males and 12 were females with a ratio of 4:1. Of all the 60 cases, 36 had a visual acuity of 20/200, 16 had a visual acuity of hand movements, and eight patients had a visual acuity of perception of light. The mean pre-operative IOP was measured as 37.01 mmHg with standard deviation (SD)± 8.82. The mean post-operative IOP was found 17.92 mmHg with SD ± 3.17. There was a mean drop of 19 mmHg of IOP postoperatively. P value was highly significant (P < 0.000). CONCLUSION: Trabeculectomy is a successful method of controlling IOP in patients with advanced glaucoma. Trabeculectomy is the method of reducing IOP in medically uncontrolled patients. A pain-free eye was associated with better quality of life in patients. A successful trabeculectomy helps to preserve the residual vision in such patients.

Vernal Keratoconjunctivitis in Kashmir: A temperate zone.

The objective of this study was to observe the clinical features of patients with vernal keratoconjunctivitis attending the Outpatient Department of a mobile eye unit, Directorate of Health Services, Jammu and Kashmir over a period of 1 year. The greater prevalence of VKC is seen in the regions with hot, humid climate, and higher load of airborne allergens. The clinical profile of this disease seems to have geographical variation. The study was conducted in the mobile eye unit, Directorate of Health Services, Kashmir, a comparatively cooler area. All the patients with vernal keratoconjunctivitis who presented to the OPD during this period were examined. The diagnosis of vernal keratoconjunctivitis was based on typical history, clinical features, and examination. All the patients with the complaints of itching, watering, and photophobia were examined. After proper history, clinical features, and ocular examination under slit lamp, the data were recorded for patients who were diagnosed with vernal keratoconjunctivitis. Of all the patients who had allergic ocular disorders, a total of 212 patients were diagnosed as cases with vernal keratoconjunctivitis. This is a non-interventional study, and the ethical clearance was obtained from the regulatory board of the hospital. The study abides by the tenets laid down in the declaration of Helsinki. During this 1-year period, 212 vernal keratoconjunctivitis patients were examined, of whom 155 (73 %) were males and 57 (27 %) were females. As per the age group, 40 % (85) of patients were in the age group of 11-15 years. 93 % (197) of patients had bilateral disease, and 7 % (15) had unilateral. It was seen that 75 % (159) had seasonal attack. Different types of disease were observed: 77 % (163) had bulbar disease, 7 % (15) had palpebral, and 16 % (34) had mixed disease. During this period, we noticed that VKC led to complications also. It was seen that 3 % (6) of patients had steroid induced glaucoma, 5 % (11) had developed cataract, 6 % (13) of patients had keratoconus, and 6 % (13) of patients had corneal scarring. Other complications were also seen. VKC is a bilateral disease. Males are affected more than females. Ocular complications were seen in around 30 % of patients. Visual impairment ranging from severe visual impairment to blindness was observed in 2 % of patients. VKC patients should be instructed to use medication under the supervision of an ophthalmologist. There is a need to assess disease severity in order to develop standardized guidelines based on the stage of vernal keratoconjunctivitis.