Herein, we investigated the protective effect of vitamin A palmitate eye gel on the ocular surface during general anesthesia. In this randomized, double-blind self-control study, we compared the protection effect of taping eyelids alone and combined with vitamin A palmitate eye gel on each participant's subjective symptoms and objective signs. In addition to a slight increase in CFS score, the STT-1 and TBUT decreased significantly, thus suggesting that those participants suffered not only from corneal abrasions but also from postoperative DED.

DED is a multifactorial disease of the ocular surface characterized by a loss of tear film homeostasis that has a vital role in providing lubrication and protection to the cornea [7]. However, postoperative DED, following general anesthesia surgery, has not drawn much attention from the surgeons. Such patients do not necessarily experience significant pain due to no instant corneal abrasions; nonetheless, they may develop progressing DED in a few days or even weeks accompanied by discomfort and associated signs, such as decreased STT and TBUT.

Thus far, reduced tear production has been considered the main pathogenic factor of postoperative DED. Tear production is controlled by the autonomic nervous system, which is dominated by the parasympathetic system. There are G protein-coupled muscarinic receptors on the surface of lacrimal gland acinar cells and conjunctival goblet cells, which are regulated by acetylcholine (Ach). Atropine is an anticholinergic drug often used in anesthesia induction and recovery, which blocks the muscarinic receptors and reduces tear secretion. In their study, Krupin et al. measured the basal tear production by standardized Schirmer strips in 20 patients, finding a significant decrease at 10, 30, and 60 min following induction of the anesthesia [6]. Decreased tear production induces the deficiency of the aqueous layer.

Recent studies showed that general anesthesia may also alter tear biochemistry [8]. Zernii et al. reported that the development of chronic postoperative DED was accompanied by a decrease in teal film stability due to the decrease in total antioxidant activity of the tear [9]. Moreover, they reported that anesthesia induced changes in the activity of tear antioxidant enzymes, including superoxide dismutase and enzymes providing homeostasis of reduced glutathione.

Batra and Bali first addressed ocular surface protection during general anesthesia in 1977 [10]. Taping the eyelid closed, the most commonly used protection method, has certain limitations, such as inconvenient pupil observation, improper pasting, or recovery stage. Finally, removing the tape may cause mechanical damage to the ocular surface. Besides, it did not provide any ingredient supplement to the tear film.

Vitamin A, as the main component of the eye gel, has an important role in regulating epithelial growth, cell proliferation, and differentiation. According to the previous study, vitamin A upregulates secretory phospholipase in A group IIA genes in human corneal conjunctival cells, increasing mucin 16 expression [11]. In the meantime, numerous population studies showed that systemic vitamin A supplementation could improve tear quality by repopulating conjunctiva goblet cells, thus increasing their density and helping corneal re-epithelization [12,13,14]. Many clinical studies have shown that topical supplementation of vitamin A is efficacious in improving ocular surface conditions [15]. A study that enrolled patients with dry eyes who were unresponsive to conventional treatments found that vitamin A ointment was effective in reducing signs and symptoms and promoting goblet cell proliferation by more than 70% [16].

The palmitate component can effectively replenish the tear film lipid layer and reduce tear evaporation. The matrix is carbomer with high viscosity, which can enhance gel protection by physical lubrication.

In the current study, the STT-1 measured at 0.5 h postoperatively in Group B was significantly decreased, while that in Group A was increased (Table 2). STT is a well-standardized test that estimates basic tear secretion. The results from Group B were consistent with the existing scientific literature on general anesthesia and tear secretion. The increase of STT-1 in Group A might have occurred for several reasons. First, mucin expression promoted by vitamin A can help further increase tear film stability. Second, carbomer, as the matrix of vitamin A, is a kind of synthetic high molecular weight polymer of acrylic acid cross-linked to a polyalkenyl polyether, which forms a liquid reservoir inside the gel after acting on the ocular surface [17]. It can slowly and permanently release drugs. In addition, gel-based artificial tear supplements can offer higher viscosity and longer retention times on the ocular surface; meanwhile, they are less sticky than oil-based formulations. Thus, the aqueous composition remained sufficient for tear film in Group A after surgery, reflecting an increase of STT-1 measured at 0.5 h postoperatively.

The results showed that the CFS score measured 0.5 h postoperatively was slightly increased in the two groups. Referring to the incidence of corneal abrasion without ocular protection [10, 18], both eye gel and typing the eyelids could effectively make a difference. The CFS score in Group A was numerically lower than in Group B, which might be due to the function of vitamin A in maintaining the health of epithelial cells. TBUT in both groups decreased at 0.5 h postoperatively, revealing no significant difference between the two groups. TBUT was the most frequently employed test of ocular surface stability, and any factor that affected the composition of the tear film could lead to a decrease. According to previous studies, vitamin A palmitate eye gel can prevent the destruction of the tear film homeostasis after ocular surgery [19, 20]. Yet, only a few studies used vitamin A palmitate eye gel to prevent postoperative DED.

Furthermore, the preoperative STT-1 and TBUT were lower than the normal level; however, only two participants declared being diagnosed with DED, suggesting the characteristic of separation of symptoms and signs. Many DED patients, especially middle-aged and older people, perimenopausal people, or users of visual display terminals, would not agree to medical intervention due to the lack of obvious symptoms, even though they developed some related signs. With a healthy ocular surface environment, the reduction of tear secretion caused by general anesthesia does not cause dyshomeostasis when solely taping the eyelid closed [21]. However, if the patient already suffered from ocular surface diseases such as DED or had shown ocular surface dyshomeostasis before the surgery, in addition to the decrease in tear secretion, this could also cause a delay in lipid layer distribution and further loss of aqueous during blinking.

The current study has certain limitations. Some participants were not fully conscious when answering the questionnaire; therefore, there is a probability that the SANDE score did not accurately show their feelings. Future research will investigate the protective effectiveness of vitamin A palmitate eye gel in lengthy surgery procedures and surgeries in lateral or prone positions.