To study expression and location of matrix metalloproteinases (MMPs) and tumor necrosis factor ␣ (TNF-␣) in glaucomatous optic nerve heads, which are known to be secreted in response to a variety of neuronal injury.Methods: Four postmortem eyes from patients with primary open-angle glaucoma, 7 eyes from patients with normal-pressure glaucoma, and 4 eyes from age-matched normal donors were studied by immunohistochemistry. The sections of the optic nerve heads were examined after immunostaining with antibodies to MMPs (MMP-1, MMP-2, and MMP-3), TNF-␣, or TNF-␣ receptor 1. Results:The intensity of the immunostaining and the number of stained cells for MMPs, TNF-␣, or TNF-␣ receptor 1 were greater in the glaucomatous optic nerve heads, particularly in eyes with normal-pressure glaucoma compared with age-matched controls. Positive immunostaining was observed in all regions of the glauco-matous optic nerve heads, but most prominently in the postlaminar region. Immunostaining was observed mainly in glial cells and their processes around the axons and blood vessels and in pial septae. Conclusion:There is increased immunostaining for MMPs, TNF-␣ and TNF-␣ receptor 1 in the glaucomatous optic nerve head, which suggests increased expression of these proteins in glaucoma and thereby implies a role in the tissue remodeling and degenerative changes seen in glaucomatous optic nerve heads.Clinical Relevance: The MMPs and TNF-␣ may be components of astroglial activation that occurs in glaucomatous optic nerve heads. The biological alterations in the expression of these proteins may play a role in the progression of glaucomatous optic neuropathy.

Aim: To investigate the rate, risk factors, clinical course, and treatment outcomes of endophthalmitis following glaucoma drainage implant (GDI) surgery. Methods: A computerised relational database search was conducted to identify all patients who were implanted with Ahmed glaucoma valve (AGV) and developed endophthalmitis following surgery at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, between 1 January 1994 and 30 November 2003. Only medical records of the patients who developed endophthalmitis were retrospectively reviewed. Results: 542 eyes of 505 patients who were on active follow up were included in the study. Endophthalmitis developed in nine (1.7%) eyes; the rate was five times higher in children than in adults. Delayed endophthalmitis (developed 6 weeks after surgery) occurred in eight of nine eyes. Conjunctival erosion overlying the AGV tube was present in six of nine eyes. Common organisms isolated in the vitreous included Haemophilus influenzae and Streptococcus species. Multiple regression analysis revealed that younger age and conjunctival erosion over the tube were significant risk factors associated with endophthalmitis. Conclusion: Endophthalmitis is a rare complication of GDI surgery that appears to be more common in children. Conjunctival dehiscence over the GDI tube seems to represent a major risk factor for endophthalmitis. Prompt surgical revision of an exposed GDI tube is highly recommended. G laucoma drainage implants (GDIs) have become an important method of controlling intraocular pressure (IOP) in patients with refractory glaucoma. Surgery with GDIs is associated with similar operative and postoperative complications that may occur after filtering surgery such as hypotomy, hyphaema, cataract, corneal decompensation, and failure to control IOP.1 In addition, several unique complications may develop with GDIs related to the presence of an implanted foreign body such as diplopia 2 and transcorneal tube erosion. 3Although endophthalmitis is a rare complication after GDI surgery, the exact rate is not known. 4 Several retrospective studies of GDIs have included a single case or a few cases of endophthalmitis resulting in rates ranging from 0.8% to 6.3%. 5-19We report the rate, clinical course, risk factors, and treatment outcomes of endophthalmitis associated with Ahmed glaucoma valve implant (New World Medical, Rancho Cucamonga, CA, USA) at one institution. METHODSThis study was reviewed and approved by the institutional review board of the King Khaled Eye Specialist Hospital (KKESH). A computerised relational database search was conducted to identify all patients who were implanted with Ahmed glaucoma valve (AGV), surgery at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, between 1 January 1994 and 30 November 2003. This group of patients was further screened to identify those who were on active follow up and had no concurrent procedures performed with the AGV implant. Patients who developed AGV related endophthalmitis in this group were included in t...

Glaucoma is a heterogeneous group of disorders that progressively lead to blindness due to loss of retinal ganglion cells and damage to the optic nerve. It is a leading cause of blindness and visual impairment worldwide. Although research in the field of glaucoma is substantial, the pathophysiologic mechanisms causing the disease are not completely understood. A wide variety of animal models have been used to study glaucoma. These include monkeys, dogs, cats, rodents, and several other species. Although these models have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. In this paper we present a summary of most of the animal models that have been developed and used for the study of the different types of glaucoma, the strengths and limitations associated with each species use, and some potential criteria to develop a suitable model.

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Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations, and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR = 25, P =2.9 × 10−14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10−8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

Background: Serum autoantibodies that cross-react with glycosaminoglycans have been proposed to play a significant role in specific tissue injury in patients with systemic autoimmune diseases. Objective: To investigate whether serum immunoreactivity to glycosaminoglycans is present in patients with glau-comawhohaveaberrantserumautoantibodiestoDNA,RNA, nuclear proteins, or retinal proteins, as proteoglycans and their glycosaminoglycan side chains are important components of the optic nerve head and its vasculature. Methods: We performed Western blotting using patient serum samples and human optic nerve head homogenates that were treated with or without specific glycosaminoglycan degrading enzymes. Monoclonal antibodies that recognize different determinants of glycosaminoglycans were used to identify specific substrate antigenicity. We compared the serum immunoreactivity to glycosaminoglycans in 60 age-matched patients with normal-pressure glaucoma, 36 patients with primary open-angle glaucoma, and 20 control subjects by enzyme-linked immunosorbent assay. In addition, immunohistochemistry was performed to compare the distribution patterns of glycosaminoglycans in the optic nerve head of postmortem eyes of agematched patients with normal-pressure glaucoma, primary open-angle glaucoma, and control subjects. Results: Western blotting demonstrated that serum samples from patients with glaucoma who have circulating autoantibodies can recognize optic nerve head proteoglycans, including chondroitin sulfate and heparan sulfate. The level of serum autoantibodies binding purified chondroitin sulfate and heparan sulfate glycosaminoglycans in an enzyme-linked immunosorbent assay was approximately 100% higher in patients with normal-pressure glaucoma than that in control subjects and approximately 50% higher than that in patients with primary open-angle glaucoma. We also observed increased immunostaining of glycosaminoglycans in the optic nerve head of eyes with glaucoma, particularly those with normal intraocular pressure, compared with control eyes. Conclusion: There are increased levels of autoantibodies recognizing glycosaminoglycans of the optic nerve head in the serum samples of some patients with glaucoma. Clinical Relevance: These autoantibodies may increase the susceptibility of the optic nerve head to damage in these patients by changing the functional properties of the lamina cribrosa, its vasculature, or both.

Patients with retinitis pigmentosa may have a measurable degree of RNFL thinning as determined by OCT. These observations could have an impact on future treatment strategies and imply that patients considered for various treatment options would benefit by an evaluation of nerve fiber layer thickness.