In the present study, we aimed to investigate the protective effect of Vitamin A Palmitate Eye Gel on ocular surface during general anesthesia. This trial was designed as a randomized double-blind self-control study, and we compared the protection effect of taping eyelid alone and combination with Vitamin A Palmitate Eye Gel on subjective symptoms and objective signs of each participant. In our study, it could be observed that in addition to CFS score increasing slightly, the STT-1 and TBUT decreased significantly, which represented 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 homeostasis of the tear film that has a vital role in providing lubrication and protection to the cornea. Postoperative DED followed by general anesthesia surgery, however, has not drawn much attention from the surgeons. Such patients may not present with significant pain due to no instant corneal abrasions. Nonetheless, they would develop progressing DED in a few days or even weeks with discomfort symptoms appearing and associated signs maintaining, such as decreased STT and TBUT.
For now, reduced tear production was considered as the main pathogenic factors of postoperative DED. Tear production is controlled by the autonomic nervous system, of which the parasympathetic system dominated. 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, as an anticholinergic drug often used in anesthesia induction and recovery, block the muscarinic receptors, and reduce tear secretion. Krupin et al. measured the basal tear production by standardized Schirmer strips in 20 patients and the results showed a significant decrease at 10, 30 and 60 minutes following induction of the anesthesia. Decreased tear production would induce the deficiency of the aqueous layer.
Recent studies showed that general anesthesia may alter tear biochemistry as well. Zernii et al. showed that the development of chronic postoperative DED was accompanied by a decrease in teal film stability, which due to the decrease in total antioxidant activity of the tear. And they observed that anesthesia induced changes in activity of tear antioxidant enzymes including superoxide dismutase and enzymes providing homeostasis of reduced glutathione.
Batra and Bali first paid attention to the ocular surface protection during general anesthesia in 1977. Taping eyelid closed, which is most commonly used protection method, has certain limitations, such as inconvenient observation of the pupil, improper pasting or recovery stage untimely removal of the tape may cause ocular surface mechanical damage. Besides, it did not provide any ingredient supplement to the tear film.
Vitamin A, as the main component of the eye gel, plays an important role in regulating epithelial growth, cell proliferation and differentiation. It was proved that in human corneal conjunctival cells, Vitamin A upregulated secretory phospholipase A group IIA genes to increase mucin 16 expression. At the meantime, numbers of population studies showed that systemic Vitamin A supplementation could improve tear quality through repopulating conjunctiva goblet cell, increasing their density and helping corneal re-epithelization[11–13]. Lots of clinical studies have proved that topical supplementation of Vitamin A was effective in ocular surface condition improvement . A study enrolled dry eye patients who were unresponsive to conventional treatments and found that Vitamin A ointment were largely effective in reducing signs and symptoms, also promoting goblet cell proliferation by more than 70%.
The palmitate component can effectively replenish tear film lipid layer and reduce tear evaporation. The matrix is carbomer with high viscosity, which can enhance the protection of gel by physical lubrication.
In the current study, it could be seen that the STT-1 measured 0.5 h postoperative in Group B was significantly decreased, but that of in Group A was increased (Fig. 2). STT is a well- standardized test which provides an estimation of basic tear secretion. The result of Group B was corresponded with the existing scientific literature on general anesthesia and tear secretion. The increase of STT-1 in Group A might have several reasons. First, mucin expression promoted by Vitamin A could help increase tear film stability further. Second, carbomer, as the matrix of Vitamin A, is kind of synthetic high molecular weight polymer of acrylic acid cross-linked to a polyalkenyl polyether, which form a liquid reservoir inside the gel after acting on the ocular surface. It could release drugs slowly and permanently. In addition, gel-based artificial tear supplements could offer higher viscosity and loner retention times on the ocular surface, meanwhile, it is less sticky than oil-based formulations. Thus, the aqueous composition still maintains sufficient for tear film in Group A after surgery, reflecting in increasing STT-1 measured 0.5 h postoperative.
The results showed that the CFS score measured 0.5 h postoperative increased slightly in two groups. Referred to the incidence of corneal abrasion without ocular protection[9, 17], both eye gel and typing the eyelids could effectively make a difference. The CFS score in Group A was numerically lower than that of in Group B, which might benefit from the function of Vitamin A in maintaining the health of epithelial cells. TBUT in both groups decreased at 0.5 h postoperative and showed no statistical difference between 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 the previous literatures, Vitamin A Palmitate Eye Gel was able to prevent the destruction of the tear film homeostasis aiming to the ocular surface that after ocular surgery or influenced by some eye drops [18, 19]. There is currently few research using Vitamin A Palmitate Eye Gel to prevent postoperative DED.
Furthermore, it could be seen from the baseline that the preoperative STT-1 and TBUT were lower than the normal level, but only two participants showed to the doctor that they were diagnosed as DED, suggesting the characteristic of separation of symptoms and signs. Many DED patients, especially middle-aged and elderly people, perimenopausal people or visual display terminal users, although related signs were developed, would not go for medical intervention because of no obvious symptoms. It was proved that with a healthy ocular surface environment, the reduction of tear secretion caused by general anesthesia would not cause dyshomeostasis under the condition of taping eyelid closed alone. However, if the patient had 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, it could also cause delay in lipid layer distribution and further loss of aqueous during blink.
The current study still showed certain limitations. Some participants were not totally conscious when answering questionnaire, therefore the SANDE score probably could not show their feelings accurately. Future research will investigate the protective effectiveness of Vitamin A Palmitate Eye Gel in long surgery procedures and the surgery in lateral or prone position.