MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension

AbstractPredicting the therapeutic response to ocular hypotensive drugs is crucial for the clinical treatment and management of glaucoma. Our aim was to identify a possible genetic contribution to the response to current pharmacological treatments of choice in a white Mediterranean population with primary open-angle glaucoma (POAG) or ocular hypertension (OH). We conducted a prospective, controlled, randomized, partial crossover study that included 151 patients of both genders, aged 18 years and older, diagnosed with and requiring pharmacological treatment for POAG or OH in one or both eyes. We sought to identify copy number variants (CNVs) associated with differences in pharmacological response, using a DNA pooling strategy of carefully phenotyped treatment responders and non-responders, treated for a minimum of 6 weeks with a beta-blocker (timolol maleate) and/or prostaglandin analog (latanoprost). Diurnal intraocular pressure reduction and comparative genome wide CNVs were analyzed. Our finding that copy number alleles of an intronic portion of the MLIP gene is a predictor of pharmacological response to beta blockers and prostaglandin analogs could be used as a biomarker to guide first-tier POAG and OH treatment. Our finding improves understanding of the genetic factors modulating pharmacological response in POAG and OH, and represents an important contribution to the establishment of a personalized approach to the treatment of glaucoma.

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DNA Copy Number Variants of Known Glaucoma Genes in Relation to Primary Open-Angle Glaucoma

Investigative Ophthalmology & Visual Science ◽

10.1167/iovs.14-15712 ◽

2014 ◽

Vol 55 (12) ◽

pp. 8251-8258 ◽

Cited By ~ 17

Author(s):

Y. Liu ◽

M. E. Garrett ◽

B. L. Yaspan ◽

J. C. Bailey ◽

S. J. Loomis ◽

...

Keyword(s):

Copy Number ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Copy Number Variants ◽

Open Angle ◽

Dna Copy Number ◽

Dna Copy Number Variants

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Publisher Correction: MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension

Scientific Reports ◽

10.1038/s41598-021-87653-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

María I. Canut ◽

Olaya Villa ◽

Bachar Kudsieh ◽

Heidi Mattlin ◽

Isabel Banchs ◽

...

Keyword(s):

Ocular Hypertension ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Open Angle ◽

Pharmacological Response

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Faculty Opinions recommendation of Omidenepag Isopropyl Versus Latanoprost in Primary Open-angle Glaucoma and Ocular Hypertension: ThePhase 3 AYAME Study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738139245.793575647 ◽

2020 ◽

Author(s):

Ingeborg Stalmans ◽

João Barbosa-Breda

Keyword(s):

Ocular Hypertension ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Open Angle

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Topical Bimatoprost Insert for Primary Open-Angle Glaucoma and Ocular Hypertension Treatment - A Phase II Controlled Study

Current Drug Delivery ◽

10.2174/1567201818666210101112256 ◽

2021 ◽

Vol 18 ◽

Author(s):

Francine Rubião ◽

Alan Cezar Faria Araújo ◽

João Bernardo Sancio ◽

Bárbara Silva Nogueira ◽

Juçara Ribeiro Franca ◽

...

Keyword(s):

Ocular Hypertension ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

T Test ◽

Controlled Study ◽

Therapeutic Drug ◽

Eye Drops ◽

Open Angle ◽

Drug Concentrations

Background: The most common treatment for primary open-angle glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and ocular hypertension (OH). Methods: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and ≤30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP≤14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, we used a two-way analysis of variance (ANOVA), Student t-test, and paired t-test. Results: Sixteen POAG and 13 OH patients with a mean age of 61 years were assessed. In both eyes, IOP reduction was similar during three weeks of follow-up (19.5±2.2 mmHg and 16.9±3.1 mmHg), insert, and eye drop, respectively; P=0.165). The percentage of IOP reduction in the third week was 30% for insert and 35% for eye drops (P=0.165). No intolerance or discomfort with the insert was reported. Among the research participants, 58% preferred the use of the insert while 25% preferred eye drops, and 17% reported no preference. Conclusions: Bimatoprost-loaded inserts showed similar efficacy to daily bimatoprost eye drops during three weeks of follow up, without major side effects. This might suggest a possible change in the daily therapeutic regimen for the treatment of POAG and OH.

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