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Subspecialties Cornea / Ocular Surface, Cataract, Glaucoma, Refractive, Retina, Practice Management, Health Economics and Policy

Time for Tears

Dry eye disease (DED), also known as keratoconjunctivitis sicca, is reported in between 5 to 50 percent of adult patients globally, with women and the elderly being at a higher risk (1). The prevalence of DED in Asia – 27.1 percent – is reported to be higher than other continents, with prevalence in India, where we practice, varying between 18.4 and 54.3 percent (2, 3, 4, 5). According to a recent observational study, the average overall incidence of DED in India was 14,593/million population – or 1.58 percent in urban populations and 1.31 percent in people living in rural areas (6).

Individuals with DED experience ocular irritation, itching, redness, mucous discharge, foreign body sensation, photosensitivity, and visual blurringwhich have an impact on their daily activities (8). DED imposes a substantial negative impact on health-related quality of life and causes considerable economic burden due to loss of work productivity (9). Multiple risk factors cause or contribute to transient dry eye symptoms (see Figure 1).

Figure 1. Risk factors for dry eye disease (1, 10).

Post-surgical DED

Surgeries to correct refractive errors, including LASIK, cataract surgery, PRK, SMILE, femtosecond lamellar extraction (FLEx), and other ophthalmic procedures (lid surgery, glaucoma surgery, keratoplasty, conjunctival surgery, vitreoretinal surgery) can all trigger dry eye symptoms transiently or exacerbate existing symptoms (11). LASIK is the most common procedure that affects tear film in approximately 50 percent of patients at 1 week, 40 percent at 1 month, 20–40 percent at 6 months, with 0.8 percent lasting more than one year (12, 13). The incidence and prevalence of DED after cataract surgery is 9.8 percent and 34 percent at four weeks and six months post-surgery, respectively – but the impact of surgery is difficult to gauge because pre-existing DED is frequent in patients with cataracts (14, 15).

Postoperative dry eye can have a negative impact on visual recovery outcomes and recovery time (16). Although the symptoms are transient in the majority of cases, it can affect the overall quality of life of the patient (11, 16). And patients may report dissatisfaction and postoperative discomfort because of dry eye symptoms (17, 18). Considering the ever-increasing number of patients undergoing the ophthalmic procedures highlighted above, it is important to understand the risk factors, mechanisms of action, and management strategies for each to reduce further complications and improve patient satisfaction and comfort (see Table 1).

Table 1. Dry eye after ophthalmic surgery.

Key: 5-FU – 5-fluorouracil; CL – contact lens; CMC – carboxymethylcellulose; HA – Hyaluronic acid; MMC – mitomycin-C; PEG/PG – polyethylene glycol/ propylene glycol.

General recommendations for other surgeries

Other ophthalmic procedures (lid surgery, glaucoma surgery, keratoplasty, conjunctival surgery, vitreoretinal surgery) can also result in dry eye symptoms. In general, pre-operative screening and management of post-surgical dry eye symptoms should be considered as critical aspects of pre- and postoperative planning. Aggressive topical lubrication, oral and topical anti-inflammatory agents, and punctal plugs can be recommended in susceptible eyes. Major intra-operative strategies include gentle manipulation, preservation of the conjunctival architecture post-peritomy, secure wound closure, minimized thermal cautery use, reduced surgical time to avoid prolonged corneal exposure, use of a corneal light shield, and frequent instillation of balanced salt solution (11).

Artificial tears in the management of post-surgical dry eye

Neurogenic inflammation caused by incision and ablation performed during refractive and cataract surgeries reduce corneal sensitivity; therefore, we need to use agents that promote healing via corneal re-epithelialization – either by increasing cells’ proliferation/migration rate, by aiding wound healing through modulating inflammation, or by facilitating cell attachment for wound closure (23). Previously published studies have reported that artificial tears can accelerate corneal re-epithelialization through different mechanisms (14, 24, 25). Artificial tears improve visual acuity, contrast sensitivity, corneal epithelial regularity, tear film stability, ocular surface stress, and also minimize desiccation and cell death by providing moisturization and lubrication to the ocular surface (26, 27, 28, 29, 30). Furthermore, peri- or post-surgical instillation of artificial tears has been shown to improve symptoms of dry eye, making them a crucial component for the management of post-surgical dry eye (11, 31). These buffered hypotonic or isotonic solutions contain viscosity-enhancing agents, osmotic agents, antioxidants, preservatives, and some inactive agents like buffers, electrolytes, and excipients (30).

Next-generation tears

Artificial tears have now progressed to advanced gel-forming drops that contain natural or synthetic polymers create a more viscous and elastic matrix in the patient’s eye than saline products, resulting in increased duration of effect. Common viscosity agents include carboxymethyl cellulose (CMC), hyaluronic acid (HA), hydroxypropyl-guar (HP-guar), and hydroxypropyl cellulose. Acting alone or in combination (for example, HP-guar-HA), these viscosity enhancers increase tear film thickness, protect against desiccation, promote tear retention at the ocular surface, protect the ocular surface, maintain physiological corneal thickness, improve goblet cell density, and relieve dry eye symptoms (30). Each hydrogel formulation acts in a different way; for example, borate/HP-guar crosslinks with natural divalent ions in the tear film to form a soft gel (very low viscosity) that is maintained between the blinks (32). In other formulations, the synergic action of different polymers can contribute towards better lubrication and retention on the ocular surface than single-polymer based artificial tears – and, therefore, result in better symptom relief (33, 34). These viscosity-enhancing agents impart a number of clinical benefits in patients experiencing post-surgical dry eye symptoms (see Table 2).

Table 2. Clinical benefits of viscosity-enhancing agents in patients with post-surgical DED.

Key: PF – preservative-free; OSDI – Ocular Surface Disease Index; TFBUT – tear-film breakup time; SH – Sodium hyaluronate; OPI- Ocular Protection Index; CIC – conjunctival impression cytology; TOSS – total ocular surface staining; IDEEL – impact of dry eye on everyday life; VAS – visual analog scale; NITBUT – non-invasive tear film breakup time; CCS – Central Corneal Sensitivity; CCT – Central corneal thickness; HLA DR -human leukocyte antigen-DR; CD3 – cluster of differentiation 3; BSS – balanced salt solution.

*Conventional therapy includes topical corticosteroids or non-steroidal anti-inflammatory drugs to manage inflammation and anti-infectives.


Beyond viscosity

Different categories of ophthalmic demulcents, including cellulose derivatives, dextran, gelatin, and liquid polyols, may also be used in artificial tear formulations. And though high molecular weight polyhydric alcohol demulcents, such as PEG/PG, do not increase viscosity, they can mimic mucin layer and protect the corneal surface when in combination with gelling agents, such as HP-guar (50). Specifically, tear formulations based on PEG/PG and HP-guar combinations have been shown to provide relief from dry eye discomfort symptoms induced or exacerbated by LASIK or cataract surgeries (45, 51). In general, ophthalmic demulcents are considered vital components of prescription formulations for DED.

A final category of compounds, osmoprotectant, protect cells under extreme osmotic stress by balancing osmotic pressure without disturbing cell metabolism. Each osmoprotectant differs in kinetics of cell entry and exit, speed of action, and acts upon different processes; however, a fixed combination of osmoprotectants can have protective synergic effect against hyperosmolarity. The most commonly used osmoprotectants in artificial tears include L-carnitine, betaine, glycerol, erythritol, and trehalose (30, 33).

No time for tears?

Regardless of the type of surgery or the peri-operative and patient-specific risk factors at play, ocular surgeries quite often aggravate or result in dry eye symptoms. In the majority of cases, dry eye symptoms are transient in nature; here, artificial tears can be considered the first-line therapy. Indeed, studies have demonstrated that dry eye symptoms were improved – and, importantly, no safety concerns were raised – when artificial tears were instilled pre- or post-operatively. However, not all artificial tears are created equal! Those that promote corneal wound healing (via corneal re-epithelialization) and offer anti-inflammatory properties appear to be best placed to reduce the incidence of post-surgical dry eye symptoms. As to the future, we would like to see further systematic, randomized clinical trials to better understand the frequency and duration of instillation needed for consistent outcomes in patients undergoing refractive correction surgery.

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About the Authors
Chandrashekhar Wavikar

Medical Director and consultant cataract and refractive surgeon at the Wavikar Eye Institute in Thane, Maharashtra, India.

Mathew Kurian

Medical Superintendent & Consultant Cataract and Refractive Surgeon at the Chaithanya Eye Institute, Palarivattom, Kerala, India.

Arindam Dey

Head CDMA and Medical Director at Alcon Laboratories India Pvt. Ltd., in Bangalore, Karnataka, India.

Prashant Sada

Medical Advisor at Alcon Laboratories India Pvt. Ltd., Bangalore, Karnataka, India.

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