Non-neovascular age-related macular degeneration with subretinal fluid.

PURPOSE: To evaluate the various patterns of subretinal fluid (SRF) in eyes with age-related macular degeneration (AMD) in the absence of macular neovascularisation (MNV) and to assess the long-term outcomes in these eyes. METHODS: This retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded. Spectral-domain optical coherence tomography (SD-OCT) was obtained at baseline and at follow-up, and qualitative and quantitative SD-OCT analysis of macular drusen including drusenoid pigment epithelial detachment (PED) and associated SRF was performed to determine anatomic outcomes. RESULTS: Forty-five eyes (45 patients) were included in this analysis. Mean duration of follow-up was 49.7±36.7 months. SRF exhibited three different morphologies: crest of fluid over the apex of the drusenoid PED, pocket of fluid at the angle of a large druse or in the crypt of confluent drusen or drape of low-lying fluid over confluent drusen. Twenty-seven (60%) of the 45 eyes with fluid displayed collapse of the associated druse or drusenoid PED and 24 (53%) of the 45 eyes developed evidence of complete or incomplete retinal pigment epithelial and outer retinal atrophy. CONCLUSION: Non-neovascular AMD with SRF is an important clinical entity to recognise to avoid unnecessary anti-vascular endothelial growth factor therapy. Clinicians should be aware that SRF can be associated with drusen or drusenoid PED in the absence of MNV and may be the result of retinal pigment epithelial (RPE) decompensation and RPE pump failure.

Maestro of regulation: Riboswitches orchestrate gene expression at the levels of translation, transcription and mRNA decay.

Riboswitches are RNA regulators that control gene expression by modulating their structure in response to metabolite binding. The study of mechanisms by which riboswitches modulate gene expression is crucial to understand how riboswitches are involved in maintaining cellular homeostasis. Previous reports indicate that riboswitches can control gene expression at the level of translation, transcription or mRNA decay. However, there are very few described examples where riboswitches regulate multiple steps in gene expression. Recent studies of a translation-regulating, TPP-dependent riboswitch have revealed that ligand binding is also involved in the control of mRNA levels. In this model, TPP binding to the riboswitch leads to the inhibition of translation, which in turn allows for Rho-dependent transcription termination. Thus, mRNA levels are indirectly controlled through ribosome occupancy. This is in contrast to other riboswitches that directly control mRNA levels by modulating the access of regulatory sequences involved in either Rho-dependent transcription termination or RNase E cleavage activity. Together, these findings indicate that riboswitches modulate both translation initiation and mRNA levels using multiple strategies that direct the outcome of gene expression.

Transcriptional pausing at the translation start site operates as a critical checkpoint for riboswitch regulation.

On the basis of nascent transcript sequencing, it has been postulated but never demonstrated that transcriptional pausing at translation start sites is important for gene regulation. Here we show that the Escherichia coli thiamin pyrophosphate (TPP) thiC riboswitch contains a regulatory pause site in the translation initiation region that acts as a checkpoint for thiC expression. By biochemically probing nascent transcription complexes halted at defined positions, we find a narrow transcriptional window for metabolite binding, in which the downstream boundary is delimited by the checkpoint. We show that transcription complexes at the regulatory pause site favour the formation of a riboswitch intramolecular lock that strongly prevents TPP binding. In contrast, cotranscriptional metabolite binding increases RNA polymerase pausing and induces Rho-dependent transcription termination at the checkpoint. Early transcriptional pausing may provide a general mechanism, whereby transient transcriptional windows directly coordinate the sensing of environmental cues and bacterial mRNA regulation.

A 2-hour information session and patient recall has minimal impact on glaucoma-treatment persistence in a mature practice.

PURPOSE: To study the impact of a 2-hour information session and 3 patients' phone calls on patient persistence with glaucoma medication. PATIENTS AND METHODS: All patients with glaucoma treatment, part of a 27-year old solo glaucoma practice, were invited to attend the information session. Patients who attended the session (n=342) were contacted by phone 1, 4, 10 months later and regular use of drops was stressed. Patients were unaware of the study. We compared the persistence of the patients before and after attending the session, and their persistence to that of patients who did not attend (n=1187). Persistence with glaucoma medication was assessed by examination of data (2002 to 2007) from a provincial medical and drug insurance database. RESULTS: Patients attending the session had glaucoma for 10 years. They had a better persistence than those who did not attend (P<0.05). Their persistence remained the same 1 year after attending the session but tended to be improved in the first 180 days (P<0.076). During the study period, there was a 4% increase in overall persistence (P<0.05). This could be due to an increase in prostaglandins prescriptions and changes in ß-blockers formulation. CONCLUSIONS: The information session and patient's recalls had a limited impact on patient persistence. This could be due to the selection of a population already persistent (78.9%). The results could have been different in less persistent patients and new patients. It could be different in another practice setting.

Follow-up of angle closure glaucoma suspects after laser iridotomy in Caucasians with normal intraocular pressure at diagnosis.

OBJECTIVE: To study the long-term outcome of Caucasian eyes with iridotrabecular trabecular apposition or peripheral anterior synechiae (PAS) and fellow eyes with narrow angles only, in eyes with intraocular pressure (IOP) <22 mm Hg at diagnosis and treated with laser peripheral iridotomy (LPI). DESIGN: Cohort study. PARTICIPANTS: Two hundred and fifty-seven Caucasian phakic patients (469 eyes) with a minimum follow-up of 2 years that had both an undilated and dilated gonioscopy after LPI. METHODS: In this retrospective cohort study, we included phakic patients with a minimum follow-up of 2 years that had both an undilated and dilated gonioscopy after LPI. Excluded were patients with pseudoexfoliation, intraocular surgery, prior acute angle-closure glaucoma or antiglaucoma medication, suspicious glaucoma disk, secondary angle closure, or iridoplasty. We censored patients after any kind of intraocular surgery. Main outcome measures where the date of IOP elevation and beginning of antiglaucoma medication. RESULTS: Four hundred and sixty-nine eyes were included. Mean follow-up was 8.5 ± 5.53 years. No apposition/PAS was observed in 84.0% of the eyes after LPI. At 10 years, 38.7% of the eyes had increased IOP and 17.3% required medication. No difference in outcomes was observed between argon and neodymium-YAG LPI or between the eyes with and without apposition/PAS before LPI. Younger patients and those with no apposition/PAS after LPI had a better prognosis (p < 0.01). CONCLUSIONS: Many angle closure glaucoma suspects developed increased IOP and required medical treatment after LPI.

Protein localization in the human eye and genetic screen of opticin.

The opticin (OPTC) gene encodes a protein that is a member of the small leucine-rich repeat protein (SLRP) family. OPTC is located on chromosome 1q31-q32 within an age-related macular degeneration (AMD) susceptibility locus. We have developed an affinity-purified N-terminal anti-opticin antibody and used it to examine opticin expression in human eye tissues. The antibody was also used for opticin protein localization in human eye sections. Immunoblots of human eye tissues detected a predominant band of approximately 62 kDa in size in iris, trabecular meshwork/ciliary body, retina, vitreous, and optic nerve. Immunohistochemical experiments revealed that opticin is specifically localized in human cornea, iris, ciliary body, vitreous, choroid and retina. Due to opticin's protein profile in the eye, we have also screened OPTC for mutations in individuals with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG) or AMD. We identified four sequence variations, all of which were observed in normal controls except for the Arg229Cys change. Three amino acid substitutions (Ile182Thr, Arg229Cys and Arg325Trp) were in residues conserved in dog, mouse, pig and human. The Arg229Cys alteration was present in a homozygous state in one individual with neovascular AMD. Examination of the other AMD afflicted family members showed that the OPTC Arg229Cys variant did not segregate with the disorder within the family. The protein localization pattern of opticin and our preliminary screen of AMD patients suggest that a larger AMD patient screen may be warranted.