Max Forbes

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 μl 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.

Retinal Detachment and Miotic Therapy

We studied a series of 34 eyes in 31 patients in whom retinal detachment occurred during miotic therapy. In 14 eyes, the duration of miotic use before the development of detachment was two months or less. Most detachments occurred in detachment-prone eyes either by virtue of myopia (62%), aphakia (24%), ipsilateral lattice degeneration (38%) or retinal pathology, in the fellow eye (50%). Virtually all detachments were rhegmatogenous. Distributions of retinal breaks are similar to the corresponding profiles in detached eyes not receiving miotics. The observed phenomena may be accounted for mechanistically, either with or without the role of miotics, so a specific causal role cannot be assigned to any given miotic in any given case. However, our data suggest that detachment-prone eyes may be at increased risk with miotic use, and thus demand careful retinal evaluation and prophylaxis when ominous peripheral symptoms are present.

Congenital ectropion uveae with glaucoma.

Congenital ectropion uveae (CEU) is a rare, nonprogressive anomaly characterized by the presence of iris pigment epithelium on the anterior surface of the iris stroma, often associated with neurofibromatosis and occasionally with other ocular anomalies. We present eight patients with unilateral CEU. Seven patients had glaucoma in the involved eye, while the eighth was a 10-week-old infant. In the two patients with bilateral glaucoma, the second eye was similar to the first, but without CEU. Three patients had neurofibromatosis, two had facial hemihypertrophy, one had Riegers anomaly, one had Prader-Willi syndrome, and one had no systemic anomalies. Two had initially been misdiagnosed as having a large pupil in the involved eye and one as having a Horners syndrome in the uninvolved eye. The finding of CEU in an infant warrants continued observation for the development of glaucoma and disorders of neural crest origin.

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.

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

Purpose Choroidal thinning has been associated with reticular pseudodrusen (RPD) and β-peripapillary atrophy (β-PPA), which have been linked to normal-tension glaucoma (NTG). This analysis sought to determine whether RPD are independently associated with β-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. β-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 β-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 β-PPA, but choroidal thickness is a confounder in this relationship. Because β-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.