Abstracts

SECTION: Physiology/Pharmacology

Purpose: The cause of decreased aqueous outflow facility (C) in the conventional outflow pathway of primary open-angle glaucoma remains unknown. Sphingosine-1-phosphate (S1P), a lysophospholipid, was previously reported to decrease C in perfused porcine and human eyes. However, the morphological correlations to this decrease remain unclear. We hypothesize that decreased C by S1P is due to a decrease in effective filtration area (EFA), which results from increased connectivity between the juxtacanalicular connective tissue (JCT) and inner wall (IW) of aqueous plexus (AP) in bovine eyes.

Methods: Freshly enucleated bovine eyes were perfused at 15mmHg to establish a stable baseline C. One eye of each pair (N=7) was then perfused with 5μM S1P and the contralateral eye with GPBS for 2 hours. All eyes were perfused with a fixed volume of fluorescent microspheres (0.002%, 0.5μm) to trace the outflow pattern. Eyes were perfusion-fixed.

Trabecular meshwork of eyes (N=4) were frontally sectioned for confocal microscopy. Total length (TL) and filtration length (FL) of AP were measured to calculate percent effective filtration length (PEFL=FL/TL). The tissue was further processed for light microscopy. JCT/IW separation (SL) was measured and calculated for percent separation length (PSL=SL/TL). Two-tailed Student's t-test was used for statistical analysis.

Results: C was significantly increased in both S1P (p=0.04) and control (p=0.002) groups compared to baseline. Although both groups exhibited washout effect, C was significantly lower in the S1P group (1.93±0.44μl/min/mmHg) compared to the control group (3.60±1.07μl/min/mmHg, p=0.005). A significantly lesser amount of tracer was observed along the JCT/IW region of S1P treated eyes, corresponding to a 62.63% decrease in PEFL compared to controls (p=0.001). A significant positive correlation was found between PEFL and the percent increase in C. Interestingly, no significant difference was found in PSL between the control (25.64±6.32%) and S1P (22.57±3.34%) groups.

Conclusions: Our results are consistent with our hypothesis that decreased C by S1P is due to a significant decrease in EFA in bovine eyes. However, the morphologic correlation was not related to increased connectivity between the JCT and IW. Further morphologic examination will be needed to understand what structural changes account for decreased EFA by S1P.

SECTION: Glaucoma

Purpose: Caloric-restriction (CR) and CR-mimetic drugs have geroprotective effects that delay or reduce Psome risks of aging. This study tested the hypothesis that the CR-mimetic drug metformin can reduce the risk of developing the late-onset trait open-angle glaucoma (OAG).

Methods: We analyzed nine years of longitudinal data from a large US health claims database (2001-2009). Diabetics, aged 40 and above with no pre-existing OAG, were monitored for incident OAG. The key predictor was exposure to metformin. A Cox proportional hazard model tested the effect of metformin on the hazard of developing OAG, adjusting for sociodemographic factors, glycemic control (HbA1c level), other diabetes medications, and other ocular and systemic conditions. The University of Michigan Institutional Review Board deemed use of this anonymized database to be exempt.

Results: Of 150,016 diabetics, 5,893 (3.9%) developed incident OAG. Use of >1,110 cumulative grams of metformin over two years was associated with a 25% reduction in relative risk of developing OAG (HR=0.75; 95% CI=0.59-0.95; p=0.017) compared with no metformin use. Every 1 gram increase in metformin was associated with a 0.01% reduced hazard of developing OAG (p=0.001). Thus someone receiving a normal dose of metformin (2 grams per day) over two years would show a 13% reduction in absolute risk of OAG relative to someone not taking metformin. When we stratified by baseline OAG risk and HbA1c level, the greatest absolute metformin-induced risk reduction was seen for those with the highest baseline risk and the highest HbA1c levels. Although HbA1c levels were associated with increased risk of OAG (HR=1.08; 95% CI=1.03-1.13; p=0.003), other hypoglycemic drugs did not reduce risk of OAG, and OAG risk-reduction in response to metformin occurred when HbA1c levels were taken into account.

Conclusions: Metformin use was associated with reduced risk of OAG. This OAG risk reduction was dose-dependent and independent of glycemic control; other diabetes medications did not confer a similar risk reduction. Thus, systems beyond glycemic control, such as neurogenesis, longevity pathways, and/or reduced inflammation may be involved in metformin-induced OAG risk-reduction. If confirmed by prospective clinical trials, these findings would offer novel treatments for this sight-threatening disease and perhaps other diseases of aging too.

The Annual Meeting Program Committee (AMPC) has established the following criteria to determine the rejection of abstracts. The decision of the AMPC is final.   

1.1 There is concern in the area of Animals as per the Statement for the Use of Animals in Ophthalmic and Visual Research.

1.2 There is concern in the area of Human Subjects as per the Helsinki Declaration or other ethics standards.

1.3 The research is not consistent with ARVO's Statement on Diversity and Open Scientific Exchange.

1.4 The abstract reports a clinical trial that does not comply with the ARVO Statement on Registering Clinical Trials.

2.1 There is concern about conflict of interest due to a lack of full disclosure of all relevant commercial relationships.

2.2 Predominantly commercial abstracts will be rejected unless they report new scientific research developments.

3.1 The abstract represents data and conclusions that have already been published.

3.2 The abstract represents data and conclusions that were presented previously at ARVO by the same group of investigators.

3.3 The abstract represents data and conclusions that are redundant with abstracts submitted in the same year by the same group of investigators.

4.1 The study uses methods that could not have led to the results reported.

4.2 The results that are reported do not support the conclusions.

4.3 The results are presented as figures or tables alone. Figures cannot be used as a substitute for the description of the results.

4.4 There is no control group or the control group is inappropriate.

4.5 The study has sample sizes that are insufficient to address the research question(s).

4.6 Abstracts of single case reports or case series will be rejected unless they provide data that significantly advance or challenge current understanding of the pathophysiology, genetics, or management of a condition.

4.7 Abstracts reporting literature reviews, meta-analyses or systematic reviews will be rejected unless the abstract includes a valid study design, demonstrable independence of sample sets, results from secondary analysis using generally accepted statistical methods to test a hypothesis and reports new conclusions that add value to the field.

5.0 Abstract results are of limited scientific value to advance the understanding or advancement of the field.

6.0 The abstract was reviewed and scored by the Annual Meeting Program Committee through a peer review process. The aggregate score did not achieve the benchmark established by the Committee.

7.0 Abstract format does not follow ARVO guidelines

8.0 The First Author did not present his/her accepted abstract in the previous year, and/or did not follow the ARVO withdrawal/replacement speaker policy. The current year's abstract from this First Author will be automatically rejected.

As of May 27, 2002

ARVO publications:  
The ARVO Board of Trustees on May 4, 2002, approved the following abstract citation policy for its journals,  Investigative Ophthalmology and Visual Science and Journal of Vision, and Translational Vision Science and Technology.

Effective with June 1, 2002 manuscript submissions, all citations to ARVO abstracts are to appear parenthetically within the text, not as bibliographic references, using the following format: (First Author name, ARVO Abstract [program number], [year]).

Abstracts for 1977-2001: (Otaishat NM, et al. IOVS 1997;38:ARVO Abstract 1415)

Abstracts for 2002 forward: (Roska BM, et al. IOVS 2002;43:ARVO E-Abstract 989)

Non-ARVO Publications:
ARVO has no control over citations to ARVO abstracts in other publications or documents, such as CVs. If abstracts are citable in those publications, the format specified by the publication must be used. Below are examples of the elements that might be included.

For abstracts prior to 2002, the following format could be used:
Otaishat NM, Li S, Naash MI, Pepperberg DR. Retinoid kinetics in the VPP mouse, a model of autosomal dominant retinitis pigmentosa [ARVO Abstract]. Invest Ophthalmol Vis Sci. 1997;38(4):S303. Abstract nr 1415.

For ARVO abstracts from 2002 forward, the following format could be used: 
Roska BM, et al. Invest Ophthalmol Vis Sci. 2002;43:ARVO E-Abstract 989

The Association for Research in Vision and Ophthalmology (ARVO) follows the ICMJE definition of a clinical trial. In order to submit an abstract to an ARVO Meeting or submit a paperfor publication in one of ARVO’s journals, you must review the definition and determine whether or not your study/research qualifies for registration. If so, please note that clinical trials require registration with a publicly accessible clinical trials registry that is a primary register of the WHO International Clinical Trials Registry Platform or in ClinicalTrials.gov. Additionally, registration must be completed before the first patient is enrolled in the clinical study.

For more information, contact clinicaltrials@arvo.org