Genetics: Now or Later?

Why it’s time to know the basics.

Inas F. Aboobakar, MD

Glaucoma Today

Genetic factors contribute to the development of all forms of early- and adult-onset glaucoma, and recent studies have identified gene variants for every form of disease.1 In coming years, this genetic information will likely have a role in clinical glaucoma care (and ophthalmology and medicine in general), so it is important to be familiar with the basics. The vision for this field is to one day be able to collect a blood sample from any given patient who presents to clinic and run a gene panel to identify the gene mutations or risk variants they carry. For early-onset forms of glaucoma, such as congenital glaucoma and juvenile open-angle glaucoma, testing could identify the causal gene mutation responsible for disease development. First-degree relatives could then be screened for that gene mutation to determine if they are also carriers and therefore warrant close monitoring. Ultimately, it may also be possible to offer these patients targeted gene therapies. For adult-onset forms of glaucoma, such as primary open-angle glaucoma (POAG), angle closure, and exfoliation glaucoma, many genes are associated with small increases in disease risk. These gene variants can be assessed in aggregate by deriving a polygenic risk score (PRS), which can provide information on an individual’s glaucoma risk relative to the general population. This may allow personalized risk assessment, monitoring, and therapy for patients with glaucoma and glaucoma suspects. In addition, understanding the specific genetic drivers for a given patient may enable us to classify them into disease subtypes. EARLY-ONSET GLAUCOMA For early-onset forms of glaucoma (patient age at onset ≤ 40 years), a single gene mutation is sufficient for disease development.

The Parasympathetic Nervous System and DED

The connection between the two suggests dry eye is more than just a disease of the eye.

Hardeep K. Kataria, OD, FAAO, and Mila Ioussifova, OD, FAAO, CNS

Modern Optometry

The parasympathetic nervous system (PNS), involved in the “rest and digest” response, and the sympathetic nervous system, involved in the “fight or flight” response, are the two main divisions of the autonomic nervous system. The PNS operates in the craniosacral and sacral segments of the central nervous system, and involves the oculomotor (III), facial (VII), glossopharyngeal (IX), and vagus (X) nerves. The primary neurotransmitters used by these nerves, acetylcholine (ACh) and vasoactive intestinal peptide (VIP), work together to promote the “rest and digest” functions of the body (eg, constricting pupils, slowing heart rate, and maintaining gut motility for digestion).1 The motor branch of the seventh nerve serves as part of the postganglionic parasympathetic pathway that innervates the lacrimal functional unit for tear production, distribution, and clearance. The lacrimal gland has mainly muscarinic ACh receptors, and the primary neurotransmitter responsible is ACh. Therefore, if we want to stimulate tear production in conditions such as aqueous-deficient dry eye disease (DED), we should focus on targeting the lacrimal gland tissue, nerve, receptor, and/or neurotransmitter.2 HOW ARE THE PNS AND DED CONNECTED? Because the PNS is mainly responsible for tear production in the lacrimal gland, when the superficial petrosal nerve is denervated, tear production is reduced by 70%. Conversely, when we stimulate the PNS, we can increase tear production.2 Additionally, the PNS plays a role in immune modulation, with the cholinergic antiinflammatory pathway linking the autonomic nervous system and the immune system, primarily through the parasympathetic nerves, especially the vagus nerve, along with ACh and its receptors. This pathway can activate and regulate immune cell functions, contributing to its antiinflammatory role and affecting the development of various autoimmune diseases.3 Anticholinergic medications, such as antihistamines and antidepressants, also downregulate the binding of ACh to its muscarinic receptor in the lacrimal gland, leading to overall reduced tear production.2 In conditions such as Sjögren syndrome, inflammation further reduces ACh release and tear production. Furthermore, the presence of muscarinic receptor antibodies that block ACh binding to the receptors may also lead to decreased tear production.4 It has been suggested that serum autoantibodies against muscarinic ACh may even serve as an early marker for Sjögren syndrome.5 Because serum ACh cannot be measured successfully, clinicians must use signs and symptoms to help guide treatment for these patients. It is worth mentioning that studies have confirmed the presence of VIP receptors in human meibomian gland acini that may be indicated in cell proliferation, and that exogenous application of VIP can stimulate goblet cell secretion; however, further data are needed to confirm the exact role of VIP in DED.6 Overall, the role of the PNS in aqueous-deficient dry eye is well established (its role in evaporative dry eye and the meibomian glands is less so).

A Global Community

Callan Navitsky, Editor-in-Chief

Glaucoma Today

Working in proximity to many trainees through YoungMD Connect, BMC’s platform for young and aspiring ophthalmologists, I regularly hear that one of the most appealing aspects of ophthalmology is its community feel. People in the field are perceived as welcoming, connected, and collegial. Although community may seem synonymous with closeness, the concept itself may be broader than that. For some, community is not defined solely by shared geography, nationality, or other social or cultural ties. In this issue of GT, ophthalmologists recount experiences in which they traveled abroad to serve and support others from different backgrounds, in different settings, and with different resources—but with a common goal to combat blindness. The anecdotes and photographs they share are snapshots of comprehensive initiatives and continuous collaborations. For example, after observing unmet needs in trabeculectomy care in Bali, Oluwatosin Smith, MD, is now working to establish a program within her home practice to address this obstacle. Annette L. Giangiacomo, MD, communicates regularly with providers she has met on past trips to remain an active part of their support team. Shawn Gulati, MD, MPH, is participating in a dedicated global ophthalmology fellowship.