Associations Between ß-Peripapillary Atrophy and Reticular Pseudodrusen in Early Age-Related Macular Degeneration.

Purpose: Choroidal thinning has been associated with reticular pseudodrusen (RPD) and ß-peripapillary atrophy (ß-PPA), which have been linked to normal-tension glaucoma (NTG). This analysis sought to determine whether RPD are independently associated with ß-PPA in early AMD patients. Secondary outcomes included the association of RPD and preexisting diagnosis of glaucoma, cup-to-disc ratio (CDR), subfoveal choroidal thickness (SFCT), and IOP. Methods: This prospective cross-sectional study examined 78 age- and sex-matched early AMD patients: 43 RPD patients (63 eyes) and 35 non-RPD patients (64 eyes). Exclusion criteria included advanced AMD, high myopia, and vitreoretinal conditions/surgery. RPD and non-RPD groups were identified by confocal scanning laser ophthalmoscopy. ß-PPA as well as CDR were graded on digital, nonstereoscopic fundus photos. SFCT was measured on spectral-domain optical coherence tomography for 69 patients (35 RPD and 34 non-RPD). IOP and glaucoma diagnosis were extracted from charts. Results: ß-PPA had a greater prevalence in RPD than non-RPD (44% vs. 19%, P = 0.002); however, this relationship was not significant when SFCT was added to the model (P = 0.150). A preexisting diagnosis of glaucoma (P = 0.156), CDR (P = 0.176), and IOP (P = 0.98) was not different between groups. Conclusions: RPD in early AMD are associated with presence of ß-PPA, but choroidal thickness is a confounder in this relationship. Because ß-PPA is a common finding in NTG, focusing on a potential shared pathway between RPD and NTG could improve the understanding of pathophysiology and expand therapies for each condition.

Intravitreal recombinant human erythropoietin: a safety study in rabbits.

PURPOSE: To evaluate the ocular safety of varying doses of a single intravitreal injection of the candidate neuroprotective agent, recombinant human erythropoietin (rhEPO). METHODS: Thirty New Zealand rabbits were divided into one of six groups: untreated controls, intravitreal saline injection, and intravitreal injections of rhEPO (100 U, 250 U, 500 U, or 1000 U). Electroretinography (ERG) was performed one day prior to injection and on post-injection days 3, 7, 14, and 21. Fluorescein angiography was done on post-injection day 28 and graded for the presence of neovascularization by a masked observer. Animals were sacrificed for histologic examination 30 days after injection. RESULTS: Except for the rhEPO 500 U group on day 21, there were no statistically significant differences in the amplitude or implicit time of the ERGs between groups or at different timepoints. Fluorescein angiography showed no evidence of neovascularization. Light microscopy showed no apparent abnormalities in retinal morphology or evidence of retinal damage compared to control groups. CONCLUSION: A single 0.1-ml intravitreal injection of rhEPO at a dose of up to 1000 U does not appear to cause adverse effects on retinal vasculature, retinal anatomy, or ERG function in albino rabbits.

Novel electrophysiological instrument for rapid and objective assessment of magnocellular deficits associated with glaucoma.

PURPOSE: To introduce a rapid and objective electrophysiological technique that can assess visual function in the magnocellular pathway, which is thought to be affected in early-stage glaucoma. METHODS: Low-contrast bright or dark isolated-checks were luminance-modulated against a static background at 10 Hz in order to drive preferentially the magnocellular ON or OFF pathway. Visual evoked potentials were recorded during 1-s epochs of stimulation and responses at the stimulus frequency were measured. Artifact rejection features ensured that eight valid runs were obtained per eye. Signal-to-noise ratios (SNR) were derived based on a multivariate statistic. In order to demonstrate its functionality, a small group of patients with glaucoma (N = 18, Snellen acuity of 20/30 or better) and control observers (N = 16) were tested. A participant failed the test if either eye yielded an SNR < or = 1. Receiver-operating-characteristic curve analysis was used to estimate the accuracy of group classification. RESULTS: The instrument was found to elicit reliable responses from control observers. For the 15% bright condition, all control observers yielded significant isolated-check VEPs (icVEPs), whereas the majority of patients failed to do so, indicating significant losses in central visual function. This condition produced the highest classification accuracy (94%), followed by the 10% dark condition (91%). CONCLUSIONS: Both ON and OFF divisions of the magnocellular pathway can be assessed rapidly through the application of the icVEP technique. This measure of central visual function may be of value in the detection of glaucomatous deficits and may complement tests of peripheral function.

Erythropoietin: a candidate neuroprotective agent in the treatment of glaucoma.

Glaucoma is a progressive optic neuropathy that is the leading cause of irreversible blindness in the world. Although methods to lower intraocular pressure are the mainstay of glaucoma therapy, there are currently no available treatment modalities targeted at neuroprotection. Erythropoietin is a hematopoietic cytokine that has been shown to possess remarkable tissue-protective properties in preclinical models of neurodegeneration. As a result, there is a growing interest to explore the neuroprotective properties of erythropoietin as a possible therapeutic agent in neuropathic diseases of the eye such as glaucoma. Initial results in animal models have been promising, but further studies are needed to fully evaluate the safety and efficacy of this candidate neuroprotective agent in clinical trials.

Intravitreal administration of erythropoietin and preservation of retinal ganglion cells in an experimental rat model of glaucoma.

PURPOSE: The aim of this pilot study was to evaluate the potential neuroprotective effect of an intravitreal injection of erythropoietin (EPO) on retinal ganglion cell (RGC) preservation in an episcleral vessel cautery-induced rat model of glaucoma. METHODS: The animals were randomly assigned into an unoperated control group (n = 11) and three experimental groups: episcleral vessel cautery only (EVC: n = 4), episcleral vessel cautery with intravitreal normal saline injection (EVC-NS; n = 5), and episcleral vessel cautery with intravitreal EPO treatment (EVC-EPO; n = 9). The intravitreal injections were limited to 5 mul containing either normal saline alone or 200 ng of EPO in normal saline administered immediately after the cautery procedure. RGCs were labeled retrogradely by FluoroGold neuron tracer 5 to 7 days prior to the collection of eyes at day 21 and counted in whole flat-mounted retinas with fluorescence microscopy. RESULTS: Compared to the RGC counts in retinal specimens from unoperated control rats (12,619 +/- 310), the corresponding RGC counts were significantly decreased in both the EVC (9116 +/- 273; p < 0.005) and EVC-NS (9489 +/- 293; p < 0.005) groups but not significantly decreased in the EVC-EPO (11,212 +/- 414; p = 0.051) treated retinas. CONCLUSIONS: A single intravitreal 200 ng dose of EPO appears to have a protective effect on RGC viability in an in vivo rat model of glaucoma. Further experimental studies are needed to confirm these preliminary results and to optimize the appropriate dose and frequency of EPO delivery in animal models of glaucoma.