Alice L. Williams

Evidence for widespread structural brain changes in glaucoma: a preliminary voxel-based MRI study.

PURPOSE To investigate structural brain changes in patients with glaucoma. METHODS High-resolution T1-weighted anatomical brain magnetic resonance images (MRI) were collected in 15 patients with glaucoma of varying severity and in 15 age-, race-, and sex-matched controls. Exclusion criteria included neurological disease, another disorder which could affect the visual field, and a score of less than 25 on the mini-mental status examination. The scans were analyzed with an automatic volumetric MRI technique to measure the volumes of 93 structures in each brain. Analyses of covariance with age as a covariate were carried out to identify structures that differed significantly between the two groups (i.e., glaucoma versus normal control). The volumes of all brain structures in the group of 15 glaucoma patients were also correlated with clinical measures of disease severity. Linear multivariate regression analyses were conducted to determine the significance of these relationships. RESULTS Five structures differed significantly between the two groups (P < 0.05). These structures included the right and left inferior occipital gyri and the right middle occipital gyrus, right inferior temporal gyrus, and right occipital lobe white matter. Interestingly, all of these structures were larger in the glaucoma group than in the control group. Within the group of glaucoma patients, 38% of all brain structures had independent associations between decreasing volume and more severe disease in multivariate regression analysis. CONCLUSIONS These results suggest that patients with glaucoma undergo widespread and complex changes in cortical brain structure and that the extent of these changes correlates with disease severity.

What do patients with glaucoma see? Visual symptoms reported by patients with glaucoma.

Background:Vision loss from glaucoma has traditionally been described as loss of “peripheral vision.” In this prospective study, we aimed to improve our clinical understanding of the visual symptoms caused by glaucoma by asking patients specific detailed questions about how they see. Methods:Patients who were clinically diagnosed with various types and stages of glaucoma were included. All had a comprehensive ocular examination, including Octopus visual field testing. Patients were excluded if they had other ocular conditions that affected their vision, including cornea, lens or retina pathologies. Patients responded to an oral questionnaire about their visual symptoms. We investigated the visual symptoms described by patients with glaucoma and correlated the severity of visual field loss with visual symptoms reported. Results:Ninety-nine patients completed the questionnaire. Most patients (76%) were diagnosed with primary open-angle glaucoma. The most common symptoms reported by all patients, including patients with early or moderate glaucoma, were needing more light and blurry vision. Patients with a greater amount of field loss (Octopus mean defect >+9.4 dB) were more likely to report difficulty seeing objects to one or both sides, as if looking through dirty glasses and trouble differentiating boundaries and colors. Conclusions:Vision loss in patients with glaucoma is not as simple as the traditional view of loss of peripheral vision. Needing more light and blurry vision were the most common symptoms reported by patients with glaucoma.

Stem cell therapy for glaucoma: Science or snake oil?

In recent years there has been substantial progress in developing stem cell treatments for glaucoma. As a downstream approach that targets the underlying susceptibility of retinal ganglion and trabecular meshwork cells, stem cell therapy has the potential to both replace lost, and protect damaged, cells by secreting neurotrophic factors. A variety of sources, including embryonic cells, adult cells derived from the central nervous system, and induced pluripotent stem cells show promise as therapeutic approaches. Even though safety concerns and ethical controversies have limited clinical implementation, some institutions have already commercialized stem cell therapy and are using direct-to-consumer advertising to attract patients with glaucoma. We review the progress of stem cell therapy and its current commercial availability.

The value of intraocular pressure asymmetry in diagnosing glaucoma

Purpose:To investigate the amount of intraocular pressure (IOP) asymmetry in a large group of ethnically diverse patients with and without glaucoma, and to delineate the risk for glaucoma which increasing amounts of IOP asymmetry confer upon the patient. Patients and Methods:Collaborative retrospective study of 326 glaucoma patients and 326 controls. Former Wills Eye Institute fellows collected single pre-treatment measurements of IOP on patients diagnosed as having definite glaucoma based on characteristic optic nerve damage and confirmatory visual field damage. Patients with a normal eye examination who had normal-appearing optic discs and no apparent glaucoma, or who had a normal eye examination in association with refractive error or cataract, were used as controls. Results:Intraocular pressure asymmetry is a significant risk factor for having glaucoma (odds ratio, 2.14; 95% confidence interval, 1.86-2.47; P<0.001). Absence of IOP asymmetry between the fellow eyes is associated with a 1% probability of having glaucoma. A difference of 3 mm Hg is associated with a 6% probability of having glaucoma, and a difference of >6 mm Hg with a 57% probability of having glaucoma. The association between IOP asymmetry and glaucoma status is significant for subjects with both elevated IOP (P=0.014) and statistically normal IOP (maximum IOP⩽21 mm Hg; P<0.001). Conclusions:Inter-eye asymmetry of IOP is a common finding in patients with glaucoma. There is a direct relationship between the amount of IOP asymmetry between the fellow eyes and the likelihood of having glaucoma.

Long-term (>8 years) evaluation of progression in patients with low-pressure glaucoma.

Purpose To describe the long-term clinical course of patients with low-pressure glaucoma (LPG) and to assess the risk factors for disease progression. Methods The Wills Eye Glaucoma Research Center retrospectively reviewed the charts of LPG patients with documented follow-up of >8 years between 2000 and 2013. Medical records were evaluated for systemic diseases, family history of glaucoma, best-corrected visual acuity, refractive error, treatments, central corneal thickness (CCT), intraocular pressure (IOP), IOP change after pupil dilation, optic disc evaluation, visual field (VF) mean deviation (MD), VF grading, and time to progression. Progression was determined when both disc and VF appeared to have worsened. Results From 850 charts classified as LPG between 2000 and 2013, 49 eyes of 49 patients were included in our analysis. The mean (± SD) follow-up time was 9.3 (± 1.9) years. Glaucoma progressed in 25 eyes and remained stable in 24 eyes over the follow-up period. Eyes with progression had higher peak IOP (p = 0.043). There was a trend towards progression in patients with thinner CCT (p = 0.085) and disc hemorrhage (p = 0.098). Estimated annual change in MD was −0.57 dB in the progressing group and −0.10 dB in the stable group (p<0.0001). Conclusions Nearly half of the patients with LPG showed glaucoma progression despite treatment after >8 years. High peak IOP was a significant risk factor for progression. Identifying patients at risk may warrant closer follow-up and more aggressive treatment in order to preserve visual function in patients with LPG.

Pilot Study Assessing the Use of High-Density Polyethylene (Su-Por®) for Tube Shunt Patch Grafts

Purpose: To assess the viability of a manufactured high-density polyethylene patch graft material (Su-Por) for prevention of tube shunt exposure. Materials and Methods: Retrospective review of the first 11 patients from the Wills Eye Hospital Glaucoma Service to receive the high-density polyethylene patch graft during tube shunt surgery. Results: Four patients (36.3%) experienced an extrusion of the Su-Por patch without a leak within 2.5 months of postoperative follow-up. All 4 patients developed either symptomatic or progressive extrusion. Operative repair was completed with Su-Por removal and replacement with a new human donor patch graft. No patient developed any sign of infection despite the extrusions. The remaining 7 patients had an uneventful postoperative course and continue to have no complications from the Su-Por patch with 9 months of follow-up. Conclusions: Given the high rate of extrusion of the Su-Por graft, this material seems to be an inadequate alternative for covering tube shunts. Harvested human tissue or other more flexible, manufactured grafts remain the standard of care for covering tube shunts.