Disruption of the complement cascade delays retinal ganglion cell death following retinal ischemia-reperfusion.

Recent reports have indicated that components of the complement cascade are synthesized during the degeneration of retinal ganglion cells (RGC) in glaucoma. While complement deposition in the retina may simply serve to aid phagocytosis of damaged RGC, activation of the complement cascade can also contribute to neuronal loss in neurodegenerative diseases. This study was designed to determine if disruption of the complement cascade affects RGC survival in a murine model of retinal ischemia-reperfusion (I/R) injury. We induced retinal ischemia in the eyes of normal mice and mice with a targeted disruption of the complement component 3 (C3) gene. Tissue was harvested 7 and 21 days after induction of I/R and retinal complement synthesis was determined by quantitative PCR and immunohistochemical methods. RGC death and associated axon loss was evaluated through histological examination of the optic nerve and retina. Our data show that retinal I/R induces the expression and deposition of complement components. C3 deficient mice clearly exhibited reduced optic nerve damage and substantial preservation of RGC 1 week after I/R when compared to normal animals (p=0.005). Three weeks after the ischemic event C3 deficient mice retained more RGC cell bodies although the degree of optic nerve damage was similar between both groups. These findings demonstrate that inhibition of the complement cascade delays optic nerve axonal and RGC degeneration in retinal I/R. It appears that injured RGC are targeted and actively destroyed through complement mediated processes. These results may have implications for the pathophysiology and clinical management of ischemic retinal conditions.

Automated segmentation of the optic disc from stereo color photographs using physiologically plausible features.

PURPOSE: To evaluate a novel automated segmentation algorithm for cup-to-disc segmentation from stereo color photographs of patients with glaucoma for the measurement of glaucoma progression. METHODS: Stereo color photographs of the optic disc were obtained by using a fixed stereo-base fundus camera in 58 eyes of 58 patients with suspected or open-angle glaucoma. Manual planimetry was performed by three glaucoma faculty members to delineate a reference standard rim and cup segmentation of all stereo pairs and by three glaucoma fellows as well. Pixel feature classification was evaluated on the stereo pairs and corresponding reference standard, by using feature computation based on simulation of photoreceptor color opponency and visual cortex simple and complex cells. An optimal subset of 12 features was used to segment all pixels in all stereo pairs, and the percentage of pixels assigned the correct class and linear cup-to-disc ratio (LCDR) estimates of the glaucoma fellows and the algorithm were compared to the reference standard. RESULTS: The algorithm was able to assign cup, rim, and background correctly to 88% of all pixels. Correlations of the LCDR estimates of glaucoma fellows with those of the reference standard were 0.73 (95% CI, 0.58-0.83), 0.81 (95% CI, 0.70-0.89), and 0.86 (95% CI, 0.78-0.91), respectively, whereas the correlation of the algorithm with the reference standard was 0.93 (95% CI, 0.89-0.96; n = 58). CONCLUSIONS: The pixel feature classification algorithm allows objective segmentation of the optic disc from conventional color stereo photographs automatically without human input. The performance of the disc segmentation and LCDR calculation of the algorithm was comparable to that of glaucoma fellows in training and is promising for objective evaluation of optic disc cupping.

Increased incidence of open-angle glaucoma among hypertensive patients: an 11-year nationwide retrospective cohort study.

OBJECTIVE: To evaluate the risk of open-angle glaucoma (OAG) among patients with systemic hypertension (HTN). METHODS: This retrospective propensity-score-matched cohort study included patients with HTN and a matched comparison cohort from the Korean National Health Insurance Service National Sample Cohort database. The HTN group was defined as patients who were prescribed antihypertensive medication, or SBP at least 140 or DBP at least 90 mmHg. The OAG group was defined as patients satisfying OAG criteria during repeated visits to an ophthalmologist. The Charlson comorbidity index was used to control for systemic conditions. Cox proportional hazard regression analysis was performed. RESULTS: OAG occurred in 2.0% (n = 1961) in the HTN group, and 1.7% (n = 1692) in the comparison group (P < 0.001). The OAG incidence rates in patients with and without HTN were 19.0 and 16.4 per 10 000 person-years, respectively. HTN was associated with increased OAG incidence [adjusted hazard ratio (HR) = 1.16, 95% confidence interval: 1.09-1.24] from our multivariate Cox model. Participants with higher SBP (adjusted HR = 1.12 for 120-139 mmHg group; and adjusted HR = 1.20 for ≥140 mmHg group) was more likely to have subsequent OAG compared with participants with less than 120 mmHg blood pressure. Participants with higher DBP (adjusted HR = 1.11 for 80-89 mmHg group: and adjusted HR = 1.07 for ≥90 mmHg group) showed similar trends as participants with less than 80 mmHg blood pressure. CONCLUSION: Patients diagnosed with HTN are more likely to experience subsequent OAG than those without HTN.

Gene expression profile of the adult human retinal ganglion cell layer.

PURPOSE: Pathophysiological events in the retinal ganglion cell layer (GCL) are a prominent feature of several optic neuropathies including glaucoma. The purpose of this study was to identify and catalog genes whose expression in the human retina is restricted to the GCL. METHODS: Laser capture microdissection (LCM) technology was used to isolate tissue from the perimacular retina of three human donors without retinal or optic nerve disease. RNA was isolated from the (1) retinal GCL and (2) the inner and outer nuclear layers of the same retina, and the gene expression profiles of both fractions were determined using Affymetrix Hu133Plus 2.0 GeneChips. Data were analyzed to identify those genes whose expression is substantially more prevalent in the GCL when compared to the outer retinal layers. Differential expression of selected genes was confirmed by real-time PCR and immunohistochemistry. RESULTS: The results show that mRNA levels of previously described ganglion cell markers, e.g. the neurofilament genes (NEFH, NEF3, or NEFL) and the Brn3a transcription factor (POU4F1), were highly enriched in the isolated GCL fraction. In contrast, transcripts for genes associated with phototransduction (RHO), photoreceptor development (NR2E3), or interphotoreceptor matrix constituents (IMPG1) were nearly absent from the GCL fraction. Using bioinformatics approaches over 80 genes were identified whose expression in the human retina appears to be limited to the GCL. CONCLUSIONS: We have successfully used LCM technology to generate gene expression profiles of highly enriched GCL fractions of the normal human retina. These data not only provide clues to the normal function of retinal ganglion cells but also serve as a resource in the development of ganglion cell specific markers or transfection vectors, and the identification of candidate genes for hereditary forms of glaucoma.

Visual field defect caused by nerve fiber layer damage associated with an internal limiting lamina defect after uneventful epiretinal membrane surgery.

PURPOSE: To report a case of visual field defect caused by damage of the nerve fiber layer associated with an internal limiting lamina defect after uneventful epiretinal membrane peeling. DESIGN: Interventional case report. METHODS: In the right eye, a 43-year-old male patient developed a nasal step and mild inferior arcuate scotoma after uneventful epiretinal membrane surgery without any associated glaucoma. Transmission electron microscopy was performed on the epiretinal membrane specimens. RESULTS: An epiretinal membrane specimen showed adhesion between epiretinal membrane and axons of nerve fiber layer in the area of the internal limiting lamina defect. CONCLUSION: Adhesion between epiretinal membrane and retinal tissue in the area of the internal limiting lamina defect may cause damage of the nerve fiber layer and visual field defect after epiretinal membrane peeling.

Iris synechia after laser goniopuncture in a patient having deep sclerectomy with a collagen implant.

Neodymium:YAG (Nd:YAG) goniopuncture is an efficient and safe treatment for low filtration through the trabeculo-Descemet's membrane after deep sclerectomy with a collagen implant (DSCI). The only reported complication of this procedure is choroidal detachment. However, we found an iris synechia in a patient whose intraocular pressure (IOP) was elevated again 1 month after Nd:YAG goniopuncture. Synechiolysis and peripheral iridectomy with Nd:YAG and argon lasers effectively removed the iris synechia, and IOP immediately dropped to the normal range. We believe that iris synechia is a potential complication that may cause elevated IOP after laser goniopuncture in patients having DSCI.

Opacification of a hydrophilic acrylic intraocular lens with exacerbation of Behçet's uveitis.

Behçet's disease is 1 of the most common causes of uveitis in the Eastern world. Its common ocular complications are uveitis, cataract, and obliteration of retinal vessels. Phacoemulsification with intraocular lens (IOL) implantation in patients with Behçet's disease is known to be a safe procedure. We managed a patient with Behçet's disease who had aggravated uveitis and opacification of a hydrophilic acrylic IOL (ACRL-C160, Ophthalmed) 4 months after cataract surgery. Recalcitrant uveitis despite maximum tolerable medication and IOL opacification with vitreous opacity necessitated an IOL exchange and trans pars plana vitrectomy. After the procedure, the eye became quiescent. However, the visual acuity was 20/200 because of the obliteration of retinal vessels.

Retinal synthesis and deposition of complement components induced by ocular hypertension.

Inappropriate activity of the complement cascade contributes to the pathophysiology of several neurodegenerative conditions. This study sought to determine if components of the complement cascade are synthesized in the retina following the development of ocular hypertension (OHT) and if complement accumulates in association with retinal ganglion cells. Toward this goal the gene expression levels of complement components 1qb (C1qb) and 3 (C3) were determined in the retina by quantitative polymerase chain reaction in human eyes with elevated intraocular pressure (IOP) and healthy retinal tissue as well as in a rat model of OHT induced by laser cauterization of the trabecular meshwork and episcleral veins. Immunohistochemical methods were employed to determine the sites of complement deposition in the retina and optic nerve head. Our data demonstrate that transcript levels for C1q and C3 are significantly elevated in retinae subjected to OHT, both in the animal model as well as in human eyes. Immunohistochemical analyses indicate that C1q and C3 accumulate specifically in the retinal ganglion cell layer and the nerve fiber layer. In addition, we demonstrate that the terminal complement complex, or membrane attack complex, is formed both in the human and rat model as a consequence of OHT. Complement activation, particularly formation of membrane attack complexes, has the potential to exacerbate ganglion cell death through bystander lysis or glial cell activation. The results show that complement activation occurs in the retina that has been subjected to elevated IOP, and may have implications in pathophysiology of glaucoma.

Purified high-dose anthocyanoside oligomer administration improves nocturnal vision and clinical symptoms in myopia subjects.

The aim of the present study was to determine the effect of purified high-dose anthocyanoside oligomer administration on nocturnal visual function and clinical symptoms in low-to-moderate myopia subjects. The study was a randomized, double-blind, placebo-controlled trial and involved sixty subjects with asthenopia and refractive errors between -1.00 and -8.00 diopters in both eyes. Thirty subjects were administered a purified high-dose anthocyanoside oligomer (100 mg tablet comprising 85 % anthocyanoside oligomer), and thirty were given a placebo in tablet form twice daily for 4 weeks. Prior to the treatment, the placebo and anthocyanoside groups were similar in terms of age and contrast sensitivity. Before and after treatment, subjects completed a questionnaire to determine their clinical symptoms and were also assessed for nocturnal visual function using contrast sensitivity testing. Questionnaire data analysis showed that, following treatment, twenty-two (73.3 %) anthocyanoside subjects showed improved symptoms, whereas only one placebo subject showed an improvement (Fisher's exact test, P<0.0001). Contrast sensitivity levels according to each cycle per degree significantly improved in the anthocyanoside group and remained stable in the placebo group. The mean contrast sensitivity change in the anthocyanoside group was 2.41 (SD) 1.91, compared with -0.66 (SD) 2.66 dB for the placebo group (unpaired Student's t test, P<0.0001). At all cycle per degree levels, contrast sensitivity changes in the anthocyanoside group were better than in the placebo group (unpaired Student's t test, P<0.05). The present data show that the administration of anthocyanoside oligomer appears to improve subjective symptoms and objective contrast sensitivity in myopia subjects with asthenopia.