Glaucoma Genetics

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There are many inheritable forms of glaucoma, both primary and secondary. While inheritance patterns and genetics are not perfectly mapped out for glaucoma, there are some basic observations that can help us screen for glaucoma among family members:

  • Many cases have an autosomal dominant inheritance pattern.
  • There is incomplete penetrance.
  • Environmental factors play a large role in the expression of glaucoma.
  • Family history is a risk factor for the development of primary open angle glaucoma (POAG).
  • 10% of glaucoma patients have siblings with glaucoma.

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Glaucoma Genes

There are many genes that have been identified in various forms of glaucoma. While genetic testing for glaucoma is not commonplace, many of these genetic markers do provide some insight into the different mechanisms and components that affect the phenotype we call glaucoma.

While this list is not comprehensive, it highlights a few of the key genotypes that we know contribute to the formation of glaucoma.

Open Angle Glaucomas (GLC1)

Many of the open angle glaucoma genes carry the GLC1 designation, with subtypes lettered following GLC1: GLC1A, GLC1B, etc. This nomenclature may help make it a bit easier to remember what type of glaucoma a particular gene encodes for. As of the American Academy of Ophthalmology’s 2016-2017 Basic and Clinical Science Course publication, there are genes listed for GLC1A-GLC1K.

Primary Open Angle Glaucoma


The GLC1A gene, which is also called the Trabecular meshwork Inducible Glucocorticoid Response/MYOCillin gene (TIGR/MYOC), encodes the TIGR/myocillin protein, which is found within the trabecular meshwork. It was the first gene identified for POAG, and is located on chromosome 1 (“first gene discovered, first subtype [GLC1A], found on chromosome 1″).

3% of POAG patients carry the GLC1A gene, and it is transmitted in an autosomal dominant fashion.


The GLC1C gene is found on chromosome 3 (“C is the 3rd letter of the English alphabet, chromosome 3”). It is associated with a late-onset primary open angle glaucoma that causes high pressure and is only moderately responsive to medications.


The GLC1G gene is found on chromosome 5. It is also known as the WDR36 gene.

Normal Tension Glaucoma

There are 2 genes that have been described in normal-tension (low pressure) glaucoma: GLC1B and GLC1E. A helpful mnemonic for remembering these genes is “BE normal,” which refers to the subtypes of the two genes, B and E.


The GLC1B gene is located on chromosome 2 (“B is the second letter of the English alphabet, chromosome 2”).


The GLC1E gene is located on chromosome 10. It encodes for the optineurin protein, which is why the other designation for this gene is OPTN (“op-ten-neurin” is a way to help remember the chromosome for this gene).

Secondary Open Angle Glaucomas

Pseudoexfoliation glaucoma (LOXL1)

Pseudoexfoliation syndrome (PXE) is a systemic condition in which there is deposition of a fibrillar material throughout the body, especially in the anterior segment, and is the most common secondary open angle glaucoma. It is associated with the LOXL1 gene, located on chromosome 15.

Pigment Dispersion Syndrome (GPDS1)

Pigment dispersion syndrome (PDS) is another fairly common cause of secondary open angle glaucoma most typically found in young myopic males. The GPDS1 gene, located on chromosome 7, is associated with PDS.

Angle Closure Glaucoma (GLC2)

There is a gene associated with primary angle closure glaucoma, termed GLC2. It is found on chromosome 11, and there are several different mutations, resulting in both autosomal dominant and autosomal recessive forms.

Congenital and Pediatric Glaucomas

Congenital Glaucomas (GLC3)

There are many causes of congenital glaucoma, with currently 4 genes identified. These genes all start with GLC3 and are lettered A-D (GLC3A, etc.). Unlike almost all of the rest of the glaucoma genes, which are inherited in an autosomal dominant pattern, congenital glaucoma genes are inherited in an autosomal recessive pattern.

One way to help remember that congenital glaucoma is GLC3 is by remembering that congenital glaucoma presents in a triad of blepharospasm, epiphora, and photophobia.


GLC3A has been identified as encoding the CYP1B1 gene and is found on chromosome 2.


GLC3B is found on chromosome 1.


GLC3C and GLC3D are found on chromosome 14.

Pediatric Glaucomas

There are several syndromes that are associated with the presentation of glaucoma in childhood. While many of these conditions are associated with anterior segment dysgenesis, this is not the only pathogenesis for glaucoma in childhood. A few of these conditions are listed here.

Nanophthalmos (NNO1, VMD2, MFRP)

There are several genes associated with the formation of nanophthalmos, all of which are found on chromosome 11. NNO1 and VMD2 are inherited in an autosomal dominant pattern, and MFRP is inherited in an autosomal recessive pattern.

I need to do some more digging, but I believe that the VMD2 gene on chromosome 11 is the same gene associated with Best vitelliform dystrophy of the retina. If so, it’s an interesting connection.

Axenfeld-Rieger Syndrome (RIEG1/PITX2, RIEG2, IRID1/FOXC1)

Axenfeld-Rieger syndrome is a spectrum of anterior segment dysgenesis that can be caused by many different genes, all inherited in an autosomal dominant pattern. RIEG1, or PITX2, is found on chromosome 4, RIEG2 is found on chromosome 13, and IRID1, or FOXC1, is found on chromosome 6.

Nail-Patella Syndrome (NPS/LMXB1)

Nail-patella syndrome (NPS) is a rare condition that primarily affects the nails, knees, elbows, and pelvis. However, it has been implicated in childhood glaucoma, and thus has been on the list of conditions associated with glaucoma. The gene associated with nail-patella syndrome is LMX1B, and is found on chromosome 9.

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Essentials To Know

Here are some key points to remember:

  • Almost all of the glaucoma genes, with the noted exception of congenital glaucomas, are inherited in an autosomal dominant pattern.
  • Congenital glaucomas (GLC3) and the MFRP variant of nanophthalmos are inherited in an autosomal recessive pattern.
  • Normal tension glaucoma genes are GLC1B and GLC1E (“BE normal”).
  • The first gene identified in open angle glaucoma, GLC1A, is located on chromosome 1 and encodes the TIGR/myocillin protein (“TIGR is number 1”).

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Summary Table

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References and Additional Reading

  1. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 10: Glaucoma. 2016-2017 ed. San Francisco: American Academy of Ophthalmology, 2016:10-11.
  2. Nail-Patella Syndrome. Genetics Home Reference, National Library of Medicine, National Institutes of Health. Website.
  3. Allingham RR, Liu Y, Rhee DJ. The genetics of primary open-angle glaucoma: a review. Exp Eye Res. 2009;88(4):837-844.
  4. Stone EM, Fingert JH, Alward WL, et al. Identification of a gene that causes primary open angle glaucoma. Science. 1997;275(5300):668-670.
  5. Wolfs RC, Klaver CC, Ramrattan RS, van Duijn CM, Hofman A, de Jong PT. Genetic risk of primary open-angle glaucoma: population-based familial aggregation study. Arch Ophthalmol. 1998;116(112):1640-1645.

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Do you have any other tips on how to remember glaucoma genetics? Leave a comment or e-mail us at!


Most Commons: General Ocular Disease And Trauma

Most commons are often tested for good reason. As we form our differential diagnoses, we need to be able to recognize what conditions are common and what conditions are uncommon. After all, what good does it do to know the differential list without having a sense of what is common and what is uncommon?

This will be another recurring series that I plan to do, as I put together my review book. Hopefully they will prove to be helpful resources!

What’s slowing me down a bit as I put together these most commons is finding references for all of this information. I promise I’m a generally trustworthy source, but I think it makes it a bit easier for you all to study based of the information I’m putting together if I can provide reputable references for the facts I put on the site.

Most Common:

Ocular abnormality1,2

Myopia (25% of US population)

Site of scleral rupture following blunt trauma3

Superonasal quadrant near the limbus

Timeframe for recurrent hyphema after original hemorrhage4

2-6 days


  1. Foster PJ, Jiang Y.  Epidemiology of myopia.  Eye (Lond).  2014;28:202-208.  doi:  10.1038/eye.2013.280.
  2. Holden B, Sankaridurg P, Smith E, Aller T, Jong M, He M.  Myopia, an underrated global challenge to vision:  where the current data takes us on myopia control.  Eye (Lond).  2014;28:142-146.  doi:  10.1038/eye.2013.256.
  3. The Eye.  In:  Basic and Clinical Science Course, Section 2:  Fundamentals and Principles of Ophthalmology.  2016-2017 ed.  San Francisco:  American Academy of Ophthalmology; 2016, 44.
  4. Ocular Pharmacotherapeutics.  In:  Basic and Clinical Science Course, Section 2:  Fundamentals and Principles of Ophthalmology.  2016-2017 ed.  San Francisco:  American Academy of Ophthalmology; 2016, 370.

Are there any other most commons in general ocular disease and trauma that I missed? Do you have any other tips? Leave a comment or e-mail me at!

Last Minute OKAP Review

Sorry it’s been so long since I’ve posted any articles!  Between acclimating to my new jobs and family obligations, I just haven’t been able to devote as much time to this site.  But don’t worry, I still plan to keep adding new content when I can!

One of the things I want to do on this site is to provide more finished “products” for you, in addition to the subject/literature reviews, test preparation and study ideas, and book reviews.  These will hopefully include charts, outlines, and other media that will help augment your studies.  I am working on several book-length projects for the site as well, including a mnemonics-style cheat book and a “textbook” of ophthalmology, with the goal of bridging the gap between the traditional high-academic works of the highly reputable textbooks and shorter-length review books.  Since those books are going to take me a considerable time to write and prepare (probably several years at the rate I’m going now), I plan to publish those for sale.  However, I still want to make the bulk of the content free, so the articles won’t be hidden behind a paywall.

I just put the final touches on my “Last Minute OKAP Review” resource, and would like to make that available to you, free of charge!  It’s a 48-page outline of ophthalmology (for reference, the American Academy of Ophthalmology’s OKAP outline is 69 pages long), with some thoughts about each subject and how I studied for the OKAP exam.

I realize it may be a bit late for many of you taking the 2017 OKAP exam, which is coming up in just under 3 weeks.  However, if you’re interested in looking at what I thought was important, you’re more than welcome to check it out!  Obviously, I cannot guarantee that any of the information in this outline will be on the test, but I can at least testify that the outline discusses most of the important topics in ophthalmology.

I’d love to get your feedback!  Because I’d like to get a more direct idea of how many people are interested in this type of resource, I am making it available by e-mail – please send me an e-mail at and I will send that to you right away!

BCSC Reading: Week 10

Week 10 Reading Assignment and Statistics

Reading Plan Book/Chapters Topics Pages Total Pages Pages/Day
AAO* Retina and Vitreous 16-End Vitreous disease, retinal surgery 289-380 91 13
Ophthalmology Review** Glaucoma 5-8 Angle closure glaucoma, childhood glaucoma, management 109-212 103 15

*The AAO reading schedule is based off the 2016-2017 BCSC series, available starting June 15, 2016.

**My reading schedule is based off the 2012-2013 BCSC series, as I do not own the new editions.

Week 10 Overview

In this week’s reading, you will finish up the Retina book if you’re following the AAO plan, and you will finish up the Glaucoma book if you’re following my plan.

The AAO Plan:

This section covers diseases of the vitreous and vitreoretinal interface.  Even though there aren’t that many conditions you need to know in this section, there are a lot of very common things you need to understand (like epiretinal membranes, macular holes, etc.).  There are also a few other diseases of the vitreous that are rarer but have systemic associations.

Ophthalmology Review Plan:

Angle closure glaucoma, childhood glaucoma, and glaucoma surgeries round out the last bit of the Glaucoma book.

Week 10 Tips and Helpful Resources

For tips and resources on reading these sections, please check out the following pages (I will be working on developing more content for this section):

BCSC Reading: Week 9

Week 9 Reading Assignment and Statistics

Reading Plan Book/Chapters Topics Pages Total Pages Pages/Day
AAO* Retina and Vitreous 8-15 ROP, choroid disease, inflammatory retinal and choroidal disease, congenital and stationary retinal disease, hereditary retinal and choroidal dystrophies, retinal degenerations associated with retinal disease, RD, diseases of vitreous 157-288 132 19
Ophthalmology Review** Glaucoma 1-4 Aqueous dynamics, glaucoma exam, open angle glaucoma 3-108 109 16

*The AAO reading schedule is based off the 2016-2017 BCSC series, available starting June 15, 2016.

**My reading schedule is based off the 2012-2013 BCSC series, as I do not own the new editions.

Week 9 Overview

In this week’s reading, some of the more obscure retinal and choroidal diseases are covered in the AAO reading, including the white dot syndromes and retinochoroidal hereditary dystrophies.  However, there are also some very commonly seen conditions, such as ROP, central serous retinochoroidopathy, and retinal detachment.  Now, since I don’t actually own a copy of the new version of the BCSC, the chapter numbering is different – so it’s very possible I am completely off base about this summary.  The first section of Glaucoma is covered if you’re following my reading plan.

The AAO Plan:

Definitely know the common conditions.  I think part of the challenge when reading a lot of these books is getting a sense of just how rare some things are in comparison to others.  Obviously diseases that have their own chapter should imply some level of importance.  ROP is another one of those conditions in which there has been and continues to be tons of research.  As technology allows babies to survive at younger and younger gestational ages, we are learning a lot more about retinal and visual development.  So in my opinion, knowing the ROP studies and how to apply them is probably an important thing to know.  Likewise, knowing the risk factors for RD and how to manage a patient with high risk for RD is important.

Ophthalmology Review Plan:

As I covered in the AAO plan when reading through Glaucoma, knowing the studies and how to apply them is very important.  This reading strategy splits up open angle glaucoma and angle closure glaucoma, which relieves some of the burden of trying to assimilate all of the secondary causes of both.

Week 9 Tips and Helpful Resources

For tips and resources on reading these sections, please check out the following pages (I will be working on developing more content for this section):

  •  This is a great resource for learning gonioscopy – a perfect time to review while reading through Glaucoma.

BCSC Reading: Week 2

Week 2 Reading Assignment and Statistics

Reading Plan Book/Chapters Topics Pages Total Pages Pages/Day
AAO* Fundamentals 5 (including Intro to Genetics)-12 Genetics, physiology of eye (tear film, cornea, iris, CB, aqueous, lens, vitreous, retina) 131-269 138 20
Ophthalmology Review** Fundamentals 9-10, 16-17 Physiology of eye (iris, CB), ocular pharmacology 253-272, 319-398 100 14

*The AAO reading schedule is based off the 2016-2017 BCSC series, available starting June 15, 2016.

**My reading schedule is based off the 2012-2013 BCSC series, as I do not own the new editions.


Since there are multiple ways to read through the BCSC, I decided to format the reading schedule based on weeks, rather than post multiple reading events.  This also allows me to reuse these events every year, instead of creating this again next year.

The two featured reading schedules are adapted from Dr. Brian T. Chan-Kai’s article on the American Academy of Ophthalmology’s website, and the reading schedule my colleagues and I used in residency.  While my reading schedule may typically seem a bit lighter, keep in mind that Dr. Chan-Kai’s schedule takes less time (31 weeks vs. 34 weeks), and goes through 12 of the 13 texts (mine covers 11 of 13).

Additionally, Dr. Chan-Kai starts the reading two weeks into the new residency year (presumably to allow for orientation and such).  I am going to start the reading schedule on this site on July 1 for simplicity, and also to allow for a few weeks of review at the end before the OKAP.  Obviously, these are all guidelines, and you can adapt the schedule however you see fit.

For someone wanting to read through the BCSC in a year to study for the ABO Written Qualifying Exam, this reading schedule should be modified, in that the written board exam doesn’t test on Section 1:  Update on General Medicine or Section 2:  Fundamentals and Principles of Ophthalmology.

Week 2 Overview

This week significantly diverges between the two reading plans.  Dr. Chan-Kai’s plan reads through each BCSC book in linear fashion, whereas the reading plan my fellow residents and I followed skipped around a little bit.  Obviously, there is no right or wrong way go about this, and there are going to be advantages and disadvantages to each (though they will be fairly minor).

The AAO Plan:

This week’s reading assignment covers ophthalmic genetics, as well as delving into the physiology of the eye.  While there are a few specific genetic diseases that are highlighted in this section, most of the genetic diseases you will read about in this section will be described in greater detail later.  The physiology sections are an interesting read, as some of this information is not mentioned to the same level of detail in the other texts (especially retinal physiology).  The short length of these chapters makes it a bit more palatable for finding a good stopping point each day.

Ophthalmology Review Plan:

This week’s reading assignment covers the iris, ciliary body, and aqueous humor, but primarily focuses on covering ocular pharmacology.  Since knowing all of the medications we commonly prescribe as ophthalmologists is pretty helpful early on in residency, we decided to reserve a lot of the ocular physiology for later as we covered the specific books.

Week 2 Tips and Helpful Resources

For tips on reading these sections, please check out the following pages (I will be working on developing more content for this section):

Review, Pediatric Ophthalmology: Phakomatoses (An Overview)

Phakomatoses are a multidisciplinary category of systemic diseases that is often tested for a multitude of reasons.  Although the incidence of these conditions is fairly low (though chances are you will see at least 1 case of many of these conditions), there are many ocular findings that need to be considered.

I’ve been debating how to organize this information in a useful manner for review for quite some time.  The subject material is pretty massive, and each condition could easily take several articles (and probably eventually will).  But I wanted to make sure there was a useful review out there on this subject before the written board exam, in case the test covers one of these conditions.

For this article, I’m going to organize the phakomatoses in a series of different tables/lists that can be used as quick references.  If you all have any suggestions or requests for putting this information together, I’d be happy to add to this resource! Continue reading “Review, Pediatric Ophthalmology: Phakomatoses (An Overview)”

Review, Glaucoma: Conditions With Increased Risk Of Glaucoma

Best of luck to all those taking the ABO’s Written Qualifying Exam this weekend! I’m on vacation this week for Spring Break, so I haven’t been able to post as many reviews as I was hoping to before the exam.

In any case, I’m going to try to post a few more generalized reviews, as I have a little bit of time before my family and I go do some more vacationy stuff.


This review is somewhat multi-disciplinary in nature. As you wrap up your reviews, one of the things I found useful was to create tons of different lists. Regardless of which test you’re studying for, there are many questions that are organized differently than how one might go about learning a particular disease. As such, I started making lists of different ways to group otherwise disparate diseases that might show up as a test question, or at least help me remember a specific feature of the disease.

Because glaucoma is a potentially sight-threatening/blinding disease, it is important to know if a particular condition is associated with glaucoma in any way, so that appropriate screening can be initiated. While the following list is by no means comprehensive, it is a list that I started putting together while I was studying for the OKAP.

Another caveat is that each individual condition will likely be featured as many individual articles in the future. For the sake of brevity (which I have a hard time doing), I am purposefully not including significant details about each disease. I am still going to try to include images of each condition, since repetition and visual pattern recognition are vital to review, and I will try to include details about the pathophysiology of glaucoma and some basic information about each condition. Hopefully this list can serve as yet another scaffold for you to remember the copious amounts of information needed for testing and clinical practice.

For those who want to skip the pictures, I made a little summary table at the bottom of the article. Hope it helps! Continue reading “Review, Glaucoma: Conditions With Increased Risk Of Glaucoma”